pharmaceutical sops

Microbiological Best Laboratory Practices

2011-12-16T23:50:00.000-08:00

Introduction

The USP finalized a series of chapters this summer. Past issues of the newsletter have discussed four of these:

<61> PMF Newsletter vol 12 no3 (March, 2006)
<62> PMF Newsletter vol 12 no4 (April, 2006)
<1111> PMF Newsletter vol 12 no6 (June, 2006)
<1072> PMF Newsletter vol 13 no2 (Feb, 2007)

There is a need to set some base level of microbiological laboratory standards. Therefore, after several rounds of discussion (stretching over a couple years), the AMB has presented a draft chapter entitled “<1117> Good Microbiological Laboratory Practices” (1). The response to this initial proposal was spirited. Comments can in from industry and FDA on this initial proposal, and a draft revision was published in 2004 (2). This revision was well-received (few comments) and made effective (with minor changes) in August of 2006 (3).

Chapter Organization

The chapter is meant to provide minimum guidance for microbiological practices in the pharmaceutical environment. As such, it is organized into topics of importance to the microbiologist:

Media Preparation and Quality Control
Maintenance of Microbiological Cultures
Maintenance of Laboratory Equipment
Laboratory Layout and Operations
Training of Personnel
Documentation
Maintenance of Laboratory Records
Interpretation of Assay Results

Media Preparation and Quality Control

The quality of work in a microbiological laboratory depends on the quality of the culture media. It is essential to use the correct media for the purpose at hand, although the correct media is not always obvious. For example, water testing is commonly done with R2A agar, but many facilities use TSA for this purpose. The recommendation is provided that the choice of media should be consistent, appropriate and justified.
The chapter spends some time on media preparation as well. The recommendations include accurate weighing of dehydrated components, the use of high quality (USP Purified) water, completely dissolving the dehydrated media or individual ingredients, and the need to control the heating of the media to avoid damaging heat-labile components of the media. Some recommendations on the labeling and packaging of media are also provided.
An entire section is devoted to the question of media storage and the effects this might have on the media quality. Excesses of heat and cold are to be guarded against, as is the potential for dehydration of poured plates. Some guidance is also provided in quality control for molten media used in pour plates.
The quality control of the media is a critical concern. Interestingly, initially some of the most passionate commentary on the chapter dealt with the “excessive” amount of space provided to media quality checks. Since the initial release in 2003, however, the harmonized Sterility Tests and the harmonized Microbial Limits Tests have both incorporated stringent media quality checks.

Maintenance of Microbiological Cultures

Second only to media, safeguarding the stock cultures is the most important component of a successful microbiology laboratory. These must be handled carefully at all times to avoid contamination.
The care of the cultures starts upon receipt. A careful stock culture curator will confirm the identity of the received cultures, even if they come from as respected a source as a national culture collection. Mistakes can happen. The use of an incorrect strain in a compendial test could bring the results of weeks or months of work into question.
The chapter reinforces the compendial preference for the “seed lot technique” in culture maintenance. Critical to this is the need to go into your containers of stock culture only once, and in restricting the number of passages. Now, it must be stated that there is nothing magic about the number 5. This number gained popularity in the compendia through its use in the Sterility Test, and has been maintained for consistency. The point to the practice is that a careful lab will safeguard the purity and identity of their stock cultures by limiting the potential for “drift” due to excessive transfers.

Maintenance of Laboratory Equipment

This section was included more for the sake of completeness than because of concerns peculiar to the microbiology laboratory. Most lab equipment in the microbiology laboratory is subject to the standard validation practices of IQ, OQ, and PQ. As is common, periodic calibration/maintenance may be required for the particular equipment based on its nature, and performance verification checks should also be performed regularly. The frequency will depend on characteristics and use of the equipment.

Laboratory Layout and Operations

The need for this section stems from the concern that too few facilities understand or plan for the separation of samples from a microbiological perspective. The success of a laboratory can be enhanced by the thoughtful separation of samples likely to have contamination from those that are expected to be sterile.

Training of Personnel

The chapter states plainly what should be common sense in recommending that microbiologists and managers in the pharmaceutical support lab should have academic training in microbiology or allied health sciences. This recommendation is in line with current best practice for biosafety as laid out in the 5th Edition of the Center for Disease Control’s (CDC) manual “Biosafety in Microbiological and Biomedical Laboratories (BMBL).” (4)
In addition to the recommendation that the microbiology staff have studied a relevant subject while in school, the proposed guidance chapter points out a fundamental link between training and the unit’s SOP system. It recommends that the SOP system should be comprehensive and serve as basis of the training program. This proposal also recommends that performance assessments be done periodically and should demonstrate competency in core activities of the lab.

Documentation and Maintenance of Laboratory Records

Like the section on equipment maintenance, this section was included only for the sake of completeness.

Interpretation of Assay Results

This section was initially entitled “OOS Investigations” it was renamed “Microbial Data Deviation Investigations” out of deference to the work underway by a PDA task force. However, during the writing process it became clear that the scope of this section was broader than merely investigations, and so the current title was settled upon almost by the process of elimination. A discussion of the inherent variability of microbiological data was necessary in this chapter. One view of good laboratory practices could be structured around determining practices that minimize variability in the microbiology lab. However, because we are dealing with such low numbers on plates (frequently less than 20 CFU/plate) and the real opportunities for human error in tests that may run over a month to completion, the microbiologist must always be aware of the role that random chance has in the data and be on guard against over-interpreting the results of a study.
This section of the proposed guidance document is intended to be both a discussion of the limitations of compendial test methodologies and a guide to developing methods of investigating test failures. It discusses the difference between a test that has failed, a test that should be invalidated and a test that should be repeated for confirmation.

Summary

The proposed chapter <1117> Good Microbiological Laboratory Practices” was developed in response to repeated requests from industry for guidance in this area. This chapter is meant to provide guidance to workers and to regulators in evaluating the operations of the QC microbiology lab.
This article is an updated version of an article by the author that originally appeared in the PMF Newsletter vol. 11 no.2 (2004).

References

USP. 2006. <1117> Microbiological Best Laboratory Practices. USP 29 Suppl 2 pp. 3804-3807.
USP. 2003. <1117> Good Microbiological Laboratory Practices. Pharmacopeial Forum 29(3):842- 850.
USP. 2004. <1117> Microbiological Best Laboratory Practices. Pharmacopeial Forum 29(3):1713- 1721.
CDC. 2007. Biosafety in Microbiological and Biomedical Laboratories (BMBL) 5th Edition http://www.cdc.gov/od/ohs/biosfty/bmbl5/ bmbl5toc.htm released to the web in February, 2007.

SOPs: Periodic Review AND Process Improvement

2011-12-16T23:36:00.000-08:00

The purpose of Standard Operating Procedures (SOPs) is to achieve consistency and uniformity in the way processes are conducted and to ensure that these processes are conducted in a manner compliant with industry and government regulations. Once an SOP is in place, it is equally important to strive for process improvement. Whether called for by changes in regulations or discovery of a “better way,” the process of updating SOPs ultimately contributes to the integrity of a pharmaceutical company and its products.

This is where periodic reviews of SOPs come into play and have a highly significant role. Regulations evolve and change and, therefore, processes must change accordingly. Reviews of SOPs (whether annual, biennial, etc.) are an opportunity to review the most current and updated regulations and incorporate changes to processes as required. It is the periodic reviews of SOPs that ensure continued compliance and contribute to a culture of ensuring patient safety, which should, of course, always be the number one goal.

Apart from regulation-based changes in processes, periodic reviews also provide the opportunity to re-evaluate a current process and seek improvement. Often times in a review of an SOP, people focus on documenting the “current” process. Often one hears much of “this is how we do it.” The question should not just be “what do we do now;” rather, the right question is really “can we do this better.” A current process may be compliant, but there may be ways to streamline it and make it more efficient, allowing the individuals and departments involved to function in a more productive manner.

Periodic reviews of SOPs are all too often viewed as cumbersome. However, they really should be viewed in a positive light as they are an opportunity to not only ensure that a process is correct, but to also determine if the process can be improved. It will always be important to keep informed of the most current regulations and change processes accordingly. However, pharmaceutical and other healthcare companies can remain ahead of the game and have a greater positive impact on patients by exceeding what is merely required by regulations and focusing on process improvement overall.

Writing Standard Operating Procedures (SOPs)

2011-12-16T23:12:00.000-08:00

SOPs are living documents that detail written instructions describing specific steps to follow in all activities under defined conditions. SOPs are necessary to ensure the continuity of processes to achieve quality performance and quality products/preparations. They form part of clinical governance, and in particular, show that pharmacists are putting in place strategies for risk management and harm minimisation.
There are different ways and formats of writing SOPs but the main aim is to get pharmacy staff to write down what they do and, at the same time, to have an opportunity to review what they are doing. The main benefits of SOPs are seen as ensuring that good practice is achieved at all times, clarifying who does what and giving guidance for locums, part time staff and new employees.
SOPs should allow for the continual improvement of standards of service, and provide evidence of commitment towards protecting patients. Additional benefits are:

Help to assure quality and consistency of service;
Help to ensure that good practice is achieved at all times;
Provide an opportunity to fully utilise the expertise of all team members;
Enable pharmacists to delegate;
Help to avoid confusion over who does what (role clarification);
Provide advice and guidance to locums and part-time staff;
They are useful tools for training new members of staff;
Provide a contribution to the audit process.

All pharmacies operate differently, and SOPs need to reflect this. However, there are some general principles that will apply. SOPs should:

Be pharmacy specific;
Be dependent on the competence of the staff working in that pharmacy;
Under normal circumstances, be applicable at all times, i.e. not dependent on the presence of the pharmacist under whose authority the procedure was prepared.

SOPs should help to ensure that, other than in exceptional circumstances, recommended procedures are followed at all times. Their introduction provides an opportunity for pharmacists to define and assess their own practice, to communicate this to staff and help to improve team-work within the pharmacy.

Who should write SOPs?

Ideally, SOPs should be written by "teams" as it is a good idea to involve staff in developing, reading and commenting on SOPs so they are happy to use them. Getting staff who are involved in specialist tasks to do the first draft of procedures can help, especially if the Charge Pharmacist has less experience in that area. Team writing accomplishes several goals in addition to producing an SOP:

It ensures that comprehensive knowledge acquired from different perspectives is applied to the SOP;
It creates "buy-in," which increases the likelihood that the SOPs will be implemented under the guidance of the writers;
Team-work trains trainers. Having participated in in-depth decision making about the SOP, writers know it intimately and are more likely to be effective trainers (coaches);
It involves people with differing roles, which helps ensure that when new and modified processes are implemented, someone goes back and updates the SOP.

SOPs should not be wordy and complicated; if short sentences or bullet points will do the trick, use them. The step-by-step parts of an SOP can be described as a numbered list or by using flow charts.

What to include

1. Write a title (with a descriptive verb) that defines the purpose of the SOP.
2. Use document reference numbers if necessary to link SOPs and add revision dates on the title or cover page and the first page of text.
3. Identify the specific points of activity for which the SOP has been written.

4. State the purpose of the SOP. Include information about process and regulatory standards. Some SOPs include both desirable and undesirable consequences.

5. Job descriptions e.g. technician, can be used to describe levels of responsibility if there is a high turnover of staff, or there are a number of part-time staff, so locums know who is responsible for what activities. Using names instead of descriptions may mean the SOP will need to be amended each time a member of staff leaves.
6. Write a "scope" statement that tells what related subjects the SOP will not cover if there is any chance someone will be confused and make a mistake. Scope statements are useful for two reasons: to focus your attention as a writer and to clarify things for a reader.
7. If any "tools" are required for following the SOP e.g. extemporaneous compounding, list these where they apply (possibly in a table).
8. Give an overview of the steps in the SOP that describes the process in terms of its major functions. Include anticipated safety, health, environmental and operational issues.
9. Define terms and concepts. If the SOP contains terms and concepts that readers may be unfamiliar with e.g. in aseptic dispensing, define these in their own paragraph so that readers (a) know that there are unusual words or concepts, and (b) can find them easily for use when needed. A long list of terms may fit better in a glossary at the beginning of a document. If you decide that a simple list of terms and definitions is better, include the list within the write up, perhaps right before the list of steps to be performed.
10. Place safety warnings, cautions and notes prominently within the SOP before the actual step to be described. Never place safety items at the end of a step.

11. List and explain the process steps in sequential order in which a SOP user should perform the steps.
For each procedure, think about the following:

Dispensing SOPs

Pharmacists are accountable for the dispensing process, but in developing and working to SOPs, should be able to benchmark current practice and ensure that systems of practice operating within their pharmacy is safe. SOPs should cover all aspects of the dispensing process, including the delivery of the medicine or product to the patient, and must comply with professional requirements applying to the dispensing process. The added-value of the pharmaceutical service i.e. the pharmacist's professional input into the assessment of the safety and appropriateness of a prescription and, in the provision of information and counselling when completed prescriptions are transferred to patients, should be explicit.
The dispensing process should be clearly defined in the SOP and it should specify which activities must be carried out personally by a pharmacist, including the clinical check (see Council Newsletter October 2006), which activities can be delegated to identified competent support staff and how the checks for accuracy are to be carried out. It is good practice for SOPs to incorporate an audit trail so that the pharmacist can determine who is responsible for each aspect of the process i.e. for each item on the prescription, the dispenser and the checking pharmacist should be clearly identified.

Keeping SOPs current

All SOPs should be numbered and should clearly marked with the date of preparation and/or date of review/amendment. They should be kept up to date and relevant at all times and should be regularly reviewed to allow for changes in practice or circumstances, for example, legislative changes or changes of staff. In the absence of any obvious changes, reviews should be undertaken at least once every two years.
When SOPs are first drafted, or when new members of staff are appointed, it is good practice to ask staff to sign to say they have read and understood them. As well as clarifying staff roles, this can also offer an opportunity for staff training and development. Pharmacists should ensure that any changes to SOPs are brought to the attention of relevant staff.

Conclusion

Writing detailed procedures and developing document management systems seem tedious and, for many, are not core competencies. However, procedures are the cornerstone of a strong quality system; they provide infrastructure; and allow for audit processes against procedures.
Creating appropriate procedures eliminates the need for interpretation by employees and ensures that procedures are being followed as intended. If developed appropriately, well-written procedures demonstrate that a pharmacy is conducting business in a controlled quality system environment. It also supports meeting the overall goal of providing the public with safe and effective medical products, which, at the end of the day, is what all pharmacies strive to achieve.
Acknowledgement: The Pharmacy Council of New Zealand kindly acknowledges the permission granted by the Royal Pharmaceutical Society of Great Britain for allowing a link to the document "Developing and implementing standard operating procedures for dispensing". This document can be viewed on http://www.rpsgb.org/pdfs/sops.pdf and PCNZ recommends visiting the website for the most up to date version.

SOPs and KISS theory can enable organisations achieve targets

2011-02-09T22:33:00.000-08:00

A LOT of advantages and merits can be achieved by having Standard Operating Procedures (SOPs) with the golden rule of Keeping It Short and Simple (KISS) in every organisation. In organisations where work is of a repetitive nature, SOPs can come in very handy and prove to be more than effective.

For example, in the aviation world, the safety and security of a flight depends highly on the crew ability to use SOPs. Theoretically, every time a pilot flies with a different pilot, there should be no difference in the way the flight was accomplished as all follow the same SOPs. In other words, aviation industry can sustain and flourish only because of SOPs.

The basic purpose of having a SOP is to break down all the tasks done in a division from simplification view point ensuring no errors are in place. Care should be taken that every member of the concerned division is well trained on understanding the SOP and adhering to the standards set out there in (this will ensure that SOPs are not merely prepared as a book keeping exercise to be kept in files without anyone reading it). Even periodic quiz should take place through inter departmental get-togethers on topics outlined in SOPs.

In organisations like military, aviation and pharmaceutical, SOPs become indispensable because every task is outlined as to how it will be done and who is going to do it.

Some of the features and big merits derived out of SOPs are as follows:

-Administration and Security of an organisation can be very effective if simplified SOPs are in place for every division and organisation listing out very clearly the numerous tasks performed and by whom.

-Modification of SOPs should be a recurring exercise so that every time a lapse or an error takes place, suitable remedial measures are taken to avoid recurrence of the same in future. Even otherwise, creeping of an error in an organisation system can be found out very easily through the SOPs listing out tasks.

-Confusion and chaos in an organisation will be to the bare minimum if not nil once all the job listings are clearly spelt out in the form of SOPs and the staff have been trained properly to understand as to which task is whose responsibility.

-Chain of tasks depending on one after another can be accomplished successfully leaving no scope for any error creeping in whatsoever.

-While framing out SOPs, care should be taken to ensure that it is written simple and not to show the writer’s skills.

Whenever Total Quality Management (TQM) matter is raised in an organisation, SOPs will always be present in the forefront. It would be a good idea if SOPs are also present or made mandatory in organisations and institutions where work carried out may not be repetitive in nature; care is needed to ensure that job listings done cover every task performed.

We often hear, due to bureaucratic delays, in Government departments work could not be done. This is mainly because there is no presence of clear cut SOPs.

Therefore, Government can consider making SOPs mandatory for every department/division/wing howsoever big or small they may be because SOPs guarantee more and more advantages with simplification of the whole processes.

Which Cleaner Should I Use?

2011-02-09T22:26:00.000-08:00

Before: Reverse osmosis membranes must be cleaned to yield required flowthrough rates - without contaminating food products.
After: After cleaning with TERGAZYME brand, diaphragm shows required drop in pressure differential - without an increase in the permeation flow.

Which Cleaner Should I Use? Use this chart to determine which cleaner is recommended for your cleaning application.

Membrane

Soil Removed/Foulant Cleaned

Iron Oxide, Metals, Aluminum, Carbonate Scale, Some Polymer, Hydroxides, Other Acid Solubles

Silt, Clay, Organic Material, Aluminum, Bio-Film, Some Polymer, Oil & Grease, Alkaline Solubles

Silt, Clay, Organic Material, Aluminum, Bio-Film, Blood, Protein Based Soils, Oil & Grease, Bio-Mass

Silt, Clay, Organic Material, Aluminum, Heavy Bio-Film, some Polymer, Oil & Grease, Alkaline Solubles

Cellulose, Acetate, & Tri-AC
RO/UF

Citranox, Citrajet

Alconox*

Liquinox*

Tergazyme*

n/a

Polyamide/aramid
R/O / NF

Citranox, Citrajet

Alconox

Liquinox

Tergazyme

Alcojet**

Polysulfone & Derivative
U/F M/F

Citranox, Citrajet

Alconox

Liquinox

Tergazyme

Alcojet

PVDF & PTFE
UF/MF

Citranox, Citrajet

Alconox

Liquinox

Tergazyme

Alcojet*

Ceramic & Stainless
UF/MF

Citranox, Citrajet

Alconox

Liquinox

Tergazyme

Alcojet

All Porous Plastic
MF

Citranox, Citrajet

Alconox

Liquinox

Tergazyme

Alcojet

Polyvinyl Alcohol
Derivative NF

Citranox, Citrajet

Alconox

Liquinox

Tergazyme

Alcojet*

Polyolefin
UF/MF

Citranox, Citrajet

Alconox

Liquinox

Tergazyme

Alcojet

* Adjust pH with Citric Acid to membrane manufacturer tolerances.
** Check with membrane manufacturer for approval.
Approved membrane configurations are: Disc & Tube, Spiral Wound, Plate & Frame and Tubular styles.
RO = Reverse Osmosis, UF = Ultrafiltration, NF = Nanofiltration, MF = Microfiltration

Pharma Clean In Place (CIP) and Standard Operating Procedures (SOPs)

2011-02-09T22:24:00.001-08:00

CIP stands for Clean-In-Place and is a method of cleaning the interior surfaces of closed systems and process equipment without dismantling the equipment. There are different types of CIP including, single pass systems and recirculation system.
The pharmaceutical industry heavily relies on clean in place (CIP) system because operators are not required to enter plant to clean, difficult to access areas can be cleaned, production time between production runs is minimized, and recycling the cleaner can reduce cost. Equipment used in pharmaceutical manufacturing must be cleaned before each use, and the cleaning procedure used must be in accordance with good manufacturing practices (GMPs). Alconox provides support to meet cGMP regulations. In fact, Alconox, Inc technical team has written The Aqueous Cleaning Handbook, where Standard Operating Procedures for CIP systems are discussed (see Chapter 7)

Zeta Potential Determination for Macroscopic Solid Samples

2011-02-07T23:15:00.000-08:00

Problem: The majority of the zetameters are based on the electrophoresis measuring principle where the zeta potential for a colloidal system is analyzed by measurement of the electrophoretic mobility of the particles. However, the measurement of the charged macroscopic surfaces is not possible with electrophoresis. Electrokinetic measurements will enable users to analyze the charged macroscopic surfaces where the zeta potential will give information regarding the adsorption and adhesion processes as well as hydrophobic and hydrophilic nature of these surfaces.

SurPASS (Surface Potential Analyzer for solid samples)

Solution: With the SurPASS, the zeta potential becomes accessible by the streaming potential or (alternatively) the streaming current method. A dilute aqueous electrolyte solution (such as 1mM KCl) is circulated through the measuring cell that contains the sample, which may be a porous sample (permeation method) or a pair of planar surfaces separated by a small gap (tangential method). The sample arrangement represents a mechanical resistance and the liquid flow generates a differential pressure between the inlet and outlet of the measuring cell. Electrical charges, which are accumulated at the interface between the solid surface and the surrounding liquid, are sheared off and accumulated on one end of the measuring cell. The generated potential difference is detected by the Ag/AgCl electrodes.

Electrochemical double layer

The zeta potential itself is defined as the electrical potential at the interface between the immobile layer of solid surface charges and the diffuse layer of counter ions and is proportional to the streaming potential coefficient dU/ dp. The complete equation for the zeta potential ζ reads

Besides the solid surface properties, the viscosity η, the dielectric coefficient ε ε0 and the electrical conductivity κ of the liquid phase contribute to the magnitude and sign of the zeta potential. The conductivity and the pH of the electrolyte are measured externally in the electrolyte reservoir. SurPASS also features a built in automatic titrator that ensures that the zeta potential can be measured as a function of varying pH or conductivity of the electrolyte. It is also possible to add small quantities of additives to detect the changes to the sample surface due to adsorption processes.
This electrokinetic analyzer enables the measurement of the zeta potential for a variety of solid samples that can range from powder, fibers and planar samples such as membranes, filters, polymers, biomaterials, silicone nitride wafers etc. These samples can be mounted into the SurPASS by using three types of measuring cells.

9 Steps on How to Perform a Laboratory Quality Audit

2011-02-07T23:12:00.000-08:00

SBS 17th Annual Conference and Exhibition

“It is strongly recommended that a laboratory conduct its own internal quality audit with sufficient frequency to assure that test analyses provide continuously reliable results. An internal audit will also provide the lab with knowledge of how well it follows its own quality program and prepare it for audients by clients.” Guidelines for Laboratory Quality Auditing, Donald C. Singer and Ronald P. Upton
Data generated by laboratories are used to make strategic decisions for all types of projects (investigation, remediation, compliance, etc.). It is important that the data are of the highest quality to avoid costly resampling and budget overruns. A laboratory audit ensures that the laboratory has quality systems in place, follows good laboratory practices, and generates data of integrity and quality.
The success of the audit is based on adequate preparation, precise performance, well documented and insightful reporting, and productive follow-up.
HOW TO PREPARE:

Define the purpose of the audit Quality audits are performed to analyze the effectiveness and implementation of programs designed to maximize the quality of goods or services delivered to the customer. The scope and technical processes involved lead to determining the needed audit team resources.
Define the scope of the audit The scope of the laboratory quality audit is defined as to limits or boundaries. Will the scope be corporate/organization-wide; the central laboratory; or a satellite laboratory? Will all analytical methodologies or a specific subset be covered? What impact will the audit scope have on the laboratory personnel and operations?
Determine the audit team resources to be used Determine what special skills/knowledge is needed among the team members to efficiently and effectively handle the scope of the audit.
Identify the authority for the audit The authority for the audit comes from the company/organization quality assurance manual, the contract for the analytical services or the request for the third party audit.
Identify the performance standards to be used The laboratory quality system has as many shapes, pieces and names for the pieces as there are authors. As a result, the audit team must evaluate the auditee’s quality system against a standard. This does not mean that all laboratory quality systems are identical or should be. The challenge is to make sure that however the auditee’s quality system is named and described; all the necessary functions are covered and implemented. The audit team will correlate the auditee’s system against the auditor’s system for equivalency of coverage.
Develop a technical understanding of the processes to be audited The audit team will function more effectively and efficiently if it has a good understanding of the laboratory’s quality system. Studying the Quality Manual and implementing procedures and historical information from prior audits (if available) prior to reaching the laboratory provides the mechanism to focus on the “mission critical” issues and develop better checklists.
Contact those to be audited The auditee is informed of the audit by the mechanism appropriate for the situation. The Lead Auditor needs to make sure it is done or do it, as the situation dictates. This initial contact provides the opportunity to establish rapport with the auditee, to work out the logistics of the audit and to acquire documents necessary for preparation, if not already available. The formal audit plan is transmitted to the auditee upon its approval.
Perform an initial evaluation of lower-tier documents to higher-level requirements This process is part of the education of the audit team. The process also provides much of the focus for the actual on-site data gathering efforts.
Develop written checklists of the data needs. The focus developed in the preceding section is documented in the development of the checklists. Where the audit program is used to cover multiple comparable laboratories, some parts of the checklists are generic. Since the main function of the checklist is to gather data, the specific issues to be examined are listed. The audit question must also be directly linked to the standard that established the requirement. This technique provides protection from the checklist being an auditor’s “wish list”. Checklists are reviewed or approved (generally by the Lead Auditor).

Preventive Maintenance of High Vacuum Pump

2011-01-18T03:32:00.003-08:00

1.0Purpose: To provide a documented procedure for Operation Planned Preventive Maintenance of High Vacuum Pump.

2.0 Objective: Operation & Preventive Maintenance of High Vacuum Pump.

3.0 Scope : This SOP is applicable for Operation & Planned Preventive Maintenance of HVP.

4.0 Responsibility :

· Primary: Technician Engineering

· Secondary: Manager Engineering

5.0 Procedure :

· Safety Precaution:

Ø Wear the necessary safety appliances during working.

Ø Wear clean & tidy uniform.

Ø Wear protective Goggles, hand gloves etc. as per work requirement.

Ø Wear safety shoes and helmets.

· Operating Procedure of HVP

Ø Before Starting the High Vacuum Pump check the oil level in oil level indicator.

Ø Start the High Vacuum Pump start the cooling water circulation.

Ø Switch on the starter. To start the vacuum pump.

Ø Check that the vacuum pump is working properly and generating sufficient vacuum.

Ø Run the pump as per required time and to stop the vacuum pump Switch Off the starter.

Ø Stop cooling water circulation.

Ø Confirm that the power supply is off from Main Switch.

Procedure and Schedule:

Sr. No.	CHECK POINTS	PROCEDURE	FREQUENCY
1.	Electrical Parts	Checking and cleaning of Starter and electrical contacts and Repairing / Replacing them if necessary.	3Months
2.	Maintaining Oil Level	Regular check up of oil level in the pump and replacing it with good oil if required (Oil Quality As specified in O/M Manual)	1Month
3	Maintenance of moisture trap.	Cleaning and maintenance of Vacuum trap.	1Month
4.	Nut Bolts and other Fasteners.	Checking and tightening the Nut Bolts and other Fasteners for proper functioning and repairing/replacing if required.	3Months
5.	Motor	Greasing and oiling of Motor bearings and other mechanical parts.	6 Months
6.	Maintenance Air Ballast System and NRV.	Checking Air Ballast System and NRV for proper functioning.	3Months
7.	V. Belt	Checking the tightness of of V-Belt. If undesired replacing it with new belt.		12Month
8.	Vacuum Gauge	Checking the efficiency and calibrating the Instrument through standard Agency.		3Months
9.	Vacuum testing.	Finally checking the vacuum on McLeod’s Gauge		1Month

Maintenance of Stainless Steel Reactor

2011-01-18T03:31:00.003-08:00

1.0 Purpose : To provide a documented procedure for Planned Preventive Maintenance of

Stainless Steel SS316 Reactor.

2.0 Objective :Preventive Maintenance of Stainless Steel SS316 Reactor.

3.0 Scope :This SOP is applicable for Planned Preventive Maintenance of Stainless Steel SS316 Reactor.

4.0 Responsibility :

· Primary: Technician Engineering

· Secondary: Manager Engineering

5.0 Procedure :

· Safety Precaution:

Ø Wear the necessary safety appliances during working.

Ø Wear clean & tidy uniform.

Ø Wear protective Goggles, hand gloves etc. as per work requirement.

Ø Wear safety shoes and helmets.

· Procedure and Schedule:

Sr. No.		CHECK POINTS	PROCEDURE		FREQUENCY
1.		Electrical Parts	Checking and cleaning of Starter and electrical contacts and Repairing / Replacing them if necessary.		6Months
2.		Gear Box.	Checking oil level in Gear box & filling if required. Replacing the oil in the gear box if required		15 Days
3.		Motor	Greasing and oiling of Motor bearings and other mechanical parts.		6 Months
4.		Steam Traps & Safety Valves	Checking the steam traps and safety valves for proper functioning and repairing/replacing if required.		3Months
5.		Nut Bolts and other Fasteners.	Checking and tightening the Nut Bolts and other Fasteners for proper functioning and repairing/replacing if required.		3Months
6.		Manhole and flush bottom Gaskets.	Changing the Gaskets of Manhole and flush bottom or when required.		3Months
7.		Condenser	Condenser Cleaning and utility flexible pipes replacement.		6Months
	8.	V-Belt.		Checking the tightness of belt and replacing if required.		6 Months
	9.	Gland Packing.		PTFE packing in the glands.		3Months.
	10.	DTI Calibration		Checking the efficiency and calibrating the Instrument		12Months
	11.	Pressure Gauge		Checking the efficiency and calibrating the Instrument		12Months

Maintenance of Tray Dryer

2011-01-18T03:31:00.001-08:00

1.0 Purpose: To provide a documented procedure for Planned Preventive Maintenance of

Tray Dryer.

2.0 Objective: Preventive Maintenance of Tray Dryer.

3.0 Scope :This SOP is applicable for Planned Preventive Maintenance of Dryer.

4.0 Responsibility :

· Primary: Technician Engineering

· Secondary: Manager Engineering

5.0 Procedure :

· Safety Precaution:

Ø Wear the necessary safety appliances during working.

Ø Wear clean & tidy uniform.

Ø Wear protective Goggles, hand gloves etc. as per work requirement.

Ø Wear safety shoes and helmets.

· Procedure and Schedule:

Sr. No.	CHECK POINTS		PROCEDURE	FREQUENCY
1.	Electrical Parts		Checking and cleaning of Starter and electrical contacts and Repairing / Replacing them if necessary.	3Months
2.	Checking Fan and fan blades for damage.		Checking Fan and fan blades for damage and corrosion.	3Months
3.	Maintenance of damper valve and exhaust line.		Checking and Cleaning of damper valve and exhaust line of the Dryer.	3Months
4.	Door Maintenance.		Checking the Door that it closes properly and sealing is Ok.	6Month
5.	Nut Bolts and other Fasteners.		Checking and tightening the Nut Bolts and other Fasteners for proper functioning and repairing/replacing if required.	3Months
6.	Motor and Blower		Greasing and oiling of Motor and blower bearings and other mechanical parts.	6 Months
7.	DTI Calibration	Checking the efficiency through Standard agency.			12Months
8.	Testing Temperature controller.	Checking the temperature controller and its function. Rectification if not as per standard.			3Months

Maintenance of Water Ring Pump.

2011-01-18T03:30:00.001-08:00

1.0 Purpose :To provide a documented procedure for Planned Preventive Maintenance of

Water Ring Pump.

2.0 Objective :Preventive Maintenance of Water Ring Pump.

3.0 Scope : This SOP is applicable for Planned Preventive Maintenance.

4.0 Responsibility :

· Primary: Technician Engineering

· Secondary: Manager Engineering

5.0 Procedure :

· Safety Precaution

Ø Wear the necessary safety appliances during working.

Ø Wear clean & tidy uniform.

Ø Wear protective Goggles, hand gloves etc. as per work requirement.

Ø Wear safety shoes and helmets.

· Operating Procedure.

Ø Before Starting the Water Ring Pump start the cooling water circulation.

Ø Switch on the starter. To start the vacuum pump.

Ø Check that the vacuum pump is working properly and generating sufficient vacuum.

Ø Run the pump as per required time and to stop the vacuum pump Switch Off the starter.

Ø Stop cooling water circulation.

Ø Confirm that the power supply is off from Main Switch.

· Maintenance Procedure and Schedule:

Sr. No.	CHECK POINTS	PROCEDURE	FREQUENCY
1.	Electrical Parts	Checking and cleaning of Starter and electrical contacts and Repairing / Replacing them if necessary.	6Months
2.	Motor	Greasing and oiling of Motor bearings and other mechanical parts.	6 Months
3.	Nut Bolts and other Fasteners.	Checking and tightening the Nut Bolts and other Fasteners for proper functioning and repairing/replacing if required.	3Months
4.	Checking Fan and fan blades for damage.	Checking Fan and fan blades for damage and corrosion.	3Months
5.	Strainer cleaning	Strainer cleaning by dismantling, and removing the scales formed and refitting after cleaning	3Months
6.	Water sump Tank Cleaning	Water sump Tank Cleaning / delaminate by Chemical treatment.	3Months.
7.	Maintenance Of Feed Water Pump	Cleaning and Over hauling of Feed Water Pump.	12Months
8.	Vacuum Gauge	Checking the efficiency and calibrating the Instrument through standard Agency.	12Months

Maintenance of Sifter

2011-01-18T03:29:00.001-08:00

1.0 Purpose : To provide a documented procedure for Planned Preventive Maintenance of

Sifter.

2.0 Objective : Preventive Maintenance of Sifter.

3.0 Scope : This SOP is applicable for Planned Preventive Maintenance of Sifter.

4.0 Responsibility :

· Primary: Technician Engineering

· Secondary: Manager Engineering

5.0 Procedure :

· Safety Precaution:

Ø Wear the necessary safety appliances during working.

Ø Wear clean & tidy uniform.

Ø Wear protective Goggles, hand gloves etc. as per work requirement.

Ø Wear safety shoes and helmets.

· Procedure and Schedule :

Sr. No.	CHECK POINTS	PROCEDURE		FREQUENCY
1.	Electrical Parts	Checking and cleaning of Starter and electrical contacts and Repairing / Replacing them if necessary.		6Months
2.	Gear Box.	Checking oil level in Gear box & filling if required. Replacing the oil in the gear box if required		15 Days
3.	Motor	Greasing and oiling of Motor bearings and other mechanical parts.		6 Months
4.	Nut Bolts and other Fasteners.	Checking and tightening the Nut Bolts and other Fasteners for proper functioning and repairing/replacing if required.		3Months
5.	Manhole and flush bottom Gaskets.	Changing the Gaskets of Manhole and flush bottom or when required.		3Months
6.	DTI Calibration		Checking the efficiency and calibrating the Instrument		12Months

Maintenance of Multimill.

2011-01-18T03:28:00.001-08:00

1.0 Purpose : To provide a documented procedure for Planned Preventive Maintenance of

Multimill.

2.0 Objective : Preventive Maintenance of Multimill.

3.0 Scope : This SOP is applicable for Planned Preventive Maintenance of Multimill.

4.0 Responsibility :

· Primary: Technician Engineering

· Secondary: Manager Engineering

5.0 Procedure :

· Safety Precaution:

Ø Wear the necessary safety appliances during working.

Ø Wear clean & tidy uniform.

Ø Wear protective Goggles, hand gloves etc. as per work requirement.

Ø Wear safety shoes and helmets.

· Procedure and Schedule :

Sr. No.	CHECK POINTS	PROCEDURE	FREQUENCY
1.	Electrical Parts	Checking and cleaning of Starter and electrical contacts and Repairing / Replacing them if necessary.	6Months
2.	Gear Box.	Checking oil level in Gear box & filling if required. Replacing the oil in the gear box if required	15 Days
3.	Motor	Greasing and oiling of Motor bearings and other mechanical parts.	6 Months
4.	Nut Bolts and other Fasteners.	Checking and tightening the Nut Bolts and other Fasteners for proper functioning and repairing/replacing if required.	3Months

Operation of Air Compressor

2011-01-18T03:27:00.003-08:00

1.0 Purpose : To provide a documented procedure for Operation of Air Compressor.

2.0 Objective : Operation of Air Compressor.

3.0 Scope : This SOP is applicable for Operation of Air Compressor.

4.0 Responsibility :

· Primary: Technician Engineering

· Secondary: Manager Engineering

5.0 Procedure :

· Before starting the compressor, check the water level of cooling tower tank, if it is low, then add more water and make it full.

· Switch ‘ON’ the “main switch” on panel of the air compressor.

· Start the cooling tower pump and fan by pushing the green button from starter.

· Remove the air bubble from the vent.

· Push the green color “Push Button” on panel to start the air compressor.

· Air compressor will start in “UNLOAD” condition and after 30 second it will start in “LOAD” condition automatically.

· During “LOAD” condition air pressure in receiver will rise, once 7 Kg/cm² air pressure is achieved, compressor will cut off automatically and run in “UNLOAD” condition.

· Open the plant air supply valve of the receiver. Air pressure in receiver will start to reduce and when air pressure is reduced to 6 kg/cm² the compressor will start on “LOAD” condition.

· This cycle of “LOAD” and “UNLOAD” will continue and it depends on air pressure requirement in the plant.

· If air pressure is not required in production then switches “OFF’ the air compressor as per method given below.

Ø Close the plant air supply valve of air receiver, allow to run the compressor in “UNLOAD” condition.

Ø Switch ‘OFF’ the “main switch” on panel of air compressor.

Ø Drain the pressure in receiver from drain valve and close the drain valve when air pressure becomes zero.

Ø Switch ‘OFF’ the cooling tower pump and fan by pushing the red colour push button on starter.

Ø Close the cooling water inlet valve of cooler and cylinder jacket.

Ø Drain the water in cylinder head jacket.

Restart The Activities After Power Failure / Breakdown

2011-01-18T03:27:00.001-08:00

1.0 Purpose : To provide a documented procedure for Procedure For Restart The Activities After Power Failure / Breakdown.

2.0 Objective : Procedure For Restart The Activities After Power Failure / Breakdown.

3.0 Scope : This SOP is applicable for. Restart The Activities After Power Failure / Breakdown.

4.0 Responsibility :

· Primary: Technician Engineering

· Secondary: Manager Engineering

5.0 Procedure :

· Power failure:

Ø Check the main power circuit panel for voltage and break down.

Ø Start the D.G. Set and check the voltage and frequency, it should be 430 V and 50 HZ.

Ø Then changeover the power supply from G.E.B. to D.G. Set for normal operation.

Ø After resuming the power supply from G.E.B. check the voltage and frequency.

Ø Before changing over power supply from D.G. Set power supply inform the critical

Ø Processing areas personnel and switch. the power supply for normal working.

· BREAKDOWN :

Ø In case of breakdown of power supply, confirm the nature of breakdown.

Ø Start the D.G. Set

Ø Check the voltage and frequency; it should be 430 V & 50 HZ.

Ø Change over the power supply from G.E.B. to D.G. Set for normal working.

Ø After attending the breakdown of power supply, restore the power supply and check the voltage and frequency of mains.

Ø Before change over the power supply from D.G. Set to G.E.B. power supply inform to critical activities area personnel for normal working.

Maintenance of Ribbon blender

2011-01-18T03:26:00.000-08:00

1.0 Purpose : To provide a documented procedure for Planned Preventive Maintenance of

Ribbon blender.

2.0 Objective: Preventive Maintenance of Ribbon blender.

3.0 Scope : This SOP is applicable for Planned Preventive Maintenance of Ribbon blender.

4.0 Responsibility :

· Primary: Technician Engineering

· Secondary: Manager Engineering

5.0 Procedure :

· Safety Precaution:

Ø Wear clean & tidy uniform.

Ø Wear protective goggles, hand gloves etc. as per work requirement.

Ø Wear safety shoes and helmets.

Ø The equipment should not be operated when the Top cover is open and Coupling guards are not in place.

Ø In operation no adjustment or lubrication should be done. This could cause serious damage to the machine and personnel.

· Design data:

1.	Material	All Contact Parts are of SS 316
2.	Electric Motors	415 V, 1440 RPM, AC motor. FLP Make: CROMPTON
3	Motor power	20 HP
3.	Start / Stop Push Button	Electric Panel Board
4.	RPM	1440 RPM
5.	Capacity	Batch Capacity 3500 KGS PER BATCH (DEPENDING UPON THE BULK DENSITY OF THE MATERIAL).
6.	Overall Dimensions	6100 mm. (L) × 1300 mm. (B) × 2206 mm. (H)
7.	Height of Charging	2206 mm.
7.	Height of Charging	2206 mm.
8.	Height of discharging	655 mm.
9.	Net Weight	2750 Kg.

· Procedure and Schedule :

Sr. No.	CHECK POINTS	PROCEDURE	FREQUENCY
1.	Electrical Parts	Checking and cleaning of motor, starter and electrical contacts and Repairing / Replacing them if necessary.	6 Months
2.	Gear Box	Checking oil level in Gear box & filling if required. Replacing the oil in the gear box if required	15 Days
3.	Motor	Greasing and oiling of Motor bearings and other mechanical parts.	6 Months
4.	Nut Bolts and other Fasteners	Checking and tightening the Nut Bolts and other Fasteners for proper functioning and repairing/replacing if required.	3 Months

· Safety Specification :

Guards	Motor and Gear Box is housed in a S.S. 304 Cover
Interlock	N.A.
Noise Level	Below decibel
Dust Generation Control	N.A.
Emergency Switch	N.A.

Types of filters in AHU as per safety and cGMP requirements

2011-01-18T03:25:00.000-08:00

1.0 Purpose: To provide cleaning instruction of various types of filters in AHU as per safety and cGMP requirements.

2.0 Objective: To provide documented procedure for cleaning instruction of various types of filters in AHU as per safety and cGMP requirements.

3.0 Scope : This SOP covers the instructions for cleaning of pre-filters and fine filters of all AHU. The SOP specifies the responsibilities of staff for the various functions outlined here under.

4.0 Responsibility :

· Primary: Technician Engineering

· Secondary: Manager Engineering

5.0 Procedure :

Ensure prior to clean:

Ø Ensure that area connected to respective AHU is not in any use by its respective user department.

Ø Intimate user department.

Ø Stop the respective AHU and remove its fuses and put a board “EQUIPMENT IS UNDER MAINTENANCE” on the MCC feeder as well as on the AHU.

Ø By pressing the local push button, ensure the respective AHU can not be started.

· Cleaning Procedure for pre-filter and fine filter:

Ø Remove the filters to be cleaned from the AHU by unscrewing all its bolts.

Ø Number the filters with marker pen as per its original location so that they can be refixed on their same location.

Ø Take all the filters to the filter cleaning room.

Ø Wear rubber gloves and eye goggles.

Ø Spray compressed air on the filter in the direction opposite to the air flow direction when the AHU is under working condition. Continue this process as per requirement of cleaning. Maintain air pressure in the range of 2 to 3 kg/cm2 g.

Ø Then clean the filters with the help of tap water.

Ø Then again spray compressed air on the filter in both the directions. Continue this spray unless all the water is removed from the filter and filter is thoroughly clean.

Ø Keep the cleaned filter on the rack for drying for 1 to 1.5 hrs.

Ø Also clean all the section of AHU like return air section, supply air section, fan – motor section, cooling coil section and all the sides of AHU by cotton dipped in potable water and final drying using dry cotton waste.

Ø Refix all the filters as per its number on their original position.

Ø Also clean the filter cleaning room.

Ø Insert the fuses of the AHU and ensure that there is no leakage by physical checking from any sides of the filters.

· SAFETY, HEALTH AND ENVIRONMENTAL ASPECTS:

Ø Before cleaning the filter:

R Wear rubber gloves and eye goggles.

R Remove the fuses of the respective AHU.

R Put a board on the MCC feeder and AHU that “AHU IS UNDER MAINTENANCE.”

Guidelines for Engineering & Maintenance

2011-01-18T03:24:00.000-08:00

1.0 Purpose : To provide guideline to ensure that different maintenance activities to support production are carried out in compliance with safety & cGMP requirement at pre-determined frequency.

2.0 Objective : To provide documented guideline to ensure that different maintenance activities to support production are carried out in compliance with safety & cGMP requirement, at pre-determined frequency.

3.0 Scope : Scope of this SOP covers all the maintenance disciplines viz. mechanical, electrical & instrumentation as well as building maintenance.

4.0 Responsibility :

· Primary: Technician Engineering

· Secondary: Manager Engineering

5.0 Procedure :

ORGANISATION & FUNCTION:

Ø The department must have a maintenance team that would perform all the maintenance functions meeting cGMP and good engineering requirements. It must also address to documentation, audits and training aspects pertaining to maintenance jobs.

Ø The Engineering Department organization must be structured to ensure that engineering functions are carried out safely, in accordance with cGMP requirements, efficiently and promptly to support production and other service areas. It must be resourced with adequate numbers of appropriately qualified and trained staff.

· MAINTENANCE STRATEGIES:

Ø Maintenance strategy must be in place for all equipments. It should consist of blend of planned (preventive) maintenance and corrective maintenance (history card).

Ø Corrective maintenance arises out of breakdowns and hence should be minimized / not repeated and filled history cards for each break down maintenance.

Ø A list must be prepared where all the equipment of the plant shall be listed. And that list would be duly reviewed by Production Manager, Engineering Manager, and General Manager and approved by QA Manager must be prepared.

Ø This list must indicate frequency of maintenance / calibration and tolerance as applicable.

· PREVENTIVE MAINTENANCE:

Ø Preventive maintenance for equipment must be scheduled on a basis appropriate for particular equipment – this should be based on statutory requirement, safety requirement, manufacturer’s recommendations, and history of the equipment.

Ø The frequency must be reviewed and changed for bringing-in improvement in performance of equipment and to build in reliability.

· CORRECTIVE MAINTENANCE:

Ø Corrective Maintenance must be carried out promptly to ensure that production down time is minimum. This shall be recorded in equipment history file.

Ø Nature of failures must be identified, understood and should be predictable. The preventive maintenance checklist must be amended by incorporating recommendations arising out of the investigation.

· PREVENTION OF CONTAMINATION AND CROSS CONTAMINATION:

Ø Prior to taking the equipment for maintenance, it must be cleaned by production staff.

Ø The post maintenance cleaning must address removal of replaced parts and materials, waste, cleaning materials and physical maintenance debris from the plant. The impact of maintenance operation such as footprints oils and greases must also be addressed.

Ø After the maintenance, the equipment, pipe, pipe fittings, etc. will be handed over to production for cleaning prior to its use. The adjacent clean equipment must be protected from contamination during maintenance operations on particular equipment

· BUILDING MAINTENANCE:

Ø Building maintenance shall be carried out as per statutory and site requirements. Documents like statutory records like painting of building, stability of building / structures etc. must be maintained to ensure that the building maintenance is carried out satisfactorily.

· VALIDATION:

Ø If maintenance service interfaces with other systems then the interfaces must be validated.

· CHANGE CONTROL:

Ø All changes must be fully documented, assessed and authorized prior to the work being carried out.

Ø In line with good documentation practice, the ELD (Engineering Line Diagram) should be updated to accurately reflect the as installed status following, a change as soon as is practicable after the change is implemented. Changes must be controlled as per the good engineering practices.

· TRAINING:

Ø All the staff shall be covered for cGMP, Safety and Job-related training as per the training procedure.

· STANDARD OPERATING PROCEDURES:

Ø Standard operating procedures must be prepared for all activities that are quality critical or safety critical or relate to key business areas. These SOPs must be prepared, reviewed & authorized and controlled in accordance with Site SOP.

Ø The SOPs must include specific maintenance instructions, lubrication details, Spares requirements, frequency of maintenance, responsibilities for carrying out the job & documentation, etc. as appropriate. The department activities must be reviewed to identify operations which need preparation of SOP and the current SOPs must be updated / reviewed as scheduled.

· AUDITS:

Ø Department audits must be carried out to monitor the Engineering aspects of departmental activities in regard to its impact on SHE, Energy Conservation and Quality matters.

· DOCUMENTATION:

Ø A separate list must be made for numbering and authorization of documents.

Ø The documents will include following:

R Forward Plan: A plan must be drawn-up for all equipment for routine maintenance as per the schedule and followed. In case of any deviation, it must be recorded and prior authorization obtained from appropriate Manager.

R Postponement of the schedule maintenance: Postponement of schedule maintenance for equipment may be required if, equipment can not be released for maintenance due production exigencies, Non-availability of external expert agency. Form requesting postponement of maintenance would be initiated by Production or Engineering Manager indicating reason for postponement and its impact and will be reviewed by Q.A. Manager and Authorized by G.M. (Works).

R Equipment file: Each equipment must have an equipment file. History of the equipment must be recorded in the equipment file. Maintenance checklist after carrying out preventive maintenance job must be filled up and filed in the Equipment history file.

R Check List: Check list must be prepared specific to each critical equipment indicating the job to be carried out. Check list will be of help to ensure that any item of maintenance has not been missed. However, the preventive maintenance checks shall not be limited to only what has been mentioned in it but surrounding site conditions must also be examined to ensure that the equipment continues to function as expected after the maintenance.

R Validation Documents: Documentation pertaining to validation would include protocol and reports for DQ, IQ and OQ activities and would be in line with the Guidelines given. Protocols and reports must also include supplier’s documentation (e.g. pressure test, calibration certificate, etc.) besides the reports generated at site.

Available Guidance and Best Practices for Conducting Forced Degradation Studies

2011-01-18T03:22:00.000-08:00

Forced degradation or stress testing is undertaken to demonstrate specificity when developing stability-indicating methods, particularly when little information is available about potential degradation products. These studies also provide information about the degradation pathways and degradation products that could form during storage. Forced degradation studies may help facilitate pharmaceutical development as well in areas such as formulation development, manufacturing, and packaging, in which knowledge of chemical behavior can be used to improve a drug product.

The available regulatory guidance provides useful definitions and general comments about degradation studies. However, guidance concerning the scope, timing, and best practices for degradation studies is very general. Various issues related to stress testing are addressed in numerous guidance documents but not always in the context of stress testing. For example, the available guidance discusses issues such as stereo chemical stability, degradation product identification thresholds, polymorphism and crystal forms, stability of (parenteral) combination products, and mass balance but does not address these issues in the context of degradation studies.

The FDA and International Conference on Harmonization (ICH) guidance provides very little information about strategies and principles for conducting forced degradation studies, including problems of poorly soluble drugs and exceptionally stable compounds. In particular, the issue of how much stress is adequate in stress testing is not addressed specifically. Overstressing a molecule can lead to degradation profiles that are not representative of real storage conditions and perhaps not relevant to method development. Therefore, stress-testing conditions should be realistic and not excessive. In this regard, it is the amount of stress that is important and not necessarily the extent of degradation. Indeed, some compounds may not degrade significantly after considerable exposure to stress conditions. Also somewhat unclear is what should be done at each development phase from both a regulatory and a scientific perspective. Although FDA does not require degradation studies for an investigational new drug (IND) application, prelimi-nary degradation studies are useful for the development of the stability-indicating methods that will be used during the clinical trials.

This article provides a practical interpretation and summary of the available guidance and some suggestions for best practices for conducting forced degradation studies.

Overview of regulatory guidance

According to the available guidance, forced degradation studies are carried out for the following reasons:

● Development and validation of stability-indicating methodology

● Determination of degradation pathways of drug substances and drug products

● Discernment of degradation products in formulations that are related to drug substances versus those that are related to non–drug substances (e.g., excipients)

● Structure elucidation of degradation products

● Determination of the intrinsic stability of a drug substance molecule Degradation studies have several defining characteristics. They are carried out in solution and/or the solid state

● Involve conditions more severe than accelerated testing (e.g., _40⁰C; 75% relative humidity; in excess of ICH light conditions; high and low pH, oxidation, etc.)

● Are typically carried out on one batch of material

● Include conditions that analyze thermolytic, hydrolytic, oxidative, and photolytic degradation mechanisms in the drug substance and drug product (as appropriate)

● are not part of the formal stability program.

Summary of requirements at the IND phase

Although the reporting of degradation studies is not required in IND applications, preliminary studies may be carried out to facilitate the development of stability-indicating methodology. Studies can be conducted on the drug substance and developmental formulations to test for degradation by thermolysis, hydrolysis, oxidation, and photolysis or to evaluate the potential chemical behavior of the active ingredient.

A draft guidance document suggests that results of one-time stress studies should be included in Phase 3 applications for INDs.

Summary of requirements for marketing application

Completed studies of the degradation of the drug substance and drug product are required at the new drug application (NDA) stage, including isolation and/or characterization of significant degradation products and a full written account of the degradation studies performed.

Drug substance-For degradation studies of a drug substance, FDA requests the following at the time of registration:

● stressing the drug substance in solution or suspension at acidic and alkaline pH and under oxidation conditions

● stressing the solid bulk drug substance at temperature and temperature–humidity conditions in excess of accelerated conditions

● stressing the drug substance photolytically in the solid state and/or in solution in excess of ICH conditions

● demonstration of the specificity of stability-indicating methods with forced-degraded samples or with the drug substance spiked with appropriate markers

● isolation and/or full characterization (by means of NMR, mass spectrometry [MS], UV analysis, etc.) of all significant degradation products if possible. Procedures for the preparation and/or isolation (where applicable) and structure determination of the degradation products should be reported. Unsuccessful attempts to identify significant degradation products should also be documented

● the chemical and physical properties of degradation products, if available

● The mechanism and kinetics of formation of each degradation product, if available. The guidance says to determine reaction kinetics “if practicable,” thereby acknowledging the difficulty in cases in which the mechanism may be complex (e.g., autoxidation).

Other issues that may be investigated but are not explicitly requested for degradation studies are the physical and chemical stability of important crystal forms, mass balance, and the formation of stereoisomers.

Drug product-The guidance specifies the following for degradation studies of the drug product at the time of registration:

● challenge methods intended for monitoring the stability of the drug product with the degraded samples or with the drug substance spiked with a mixture of known degradation products

● isolation and characterization of significant degradation products, if possible. The identity and chemical structure, procedure for isolation and purification, mechanism of formation (including order of reaction), and chemical and physical

properties should be reported, if available. These degradation products include any drug substance–related compounds such as drug substance degradation products, drug substance–excipient degradation products, drug substance– extractive degradation products, and so forth.

● distinction between degradation products that are related to drug substances and those related to non–drug substances

● photolysis of the drug product in excess of ICH light conditions

Information requested in the submission. The available guidance explicitly requests the following in the NDA documentation:

● for degradation products: identity and structure; procedure for isolation (where applicable) and characterization; mechanism of formation, including order of reaction; and physical and chemical properties

● information about stress testing of the drug substance and drug product (the guidance does not state specifically what information is required).

At the time of this writing (May 2001), more-specific guidance for the reporting of stress testing was found in FDA draft guidance documents dealing with stability and method validation. According to these documents, the applicant should provide

● degradation pathways of the drug substance, alone and in the drug product

● a discussion of the possible formation of polymorphic and enantiomeric substances; the possible formation of any stereoisomer’s is implied

● data showing that neither the freshly prepared nor the degraded placebo interferes with the quantitation of the active ingredient

● data from stress studies of the drug substance and drug product demonstrating the specificity of the assay and analytical procedures for degradation products. These data may take the form of representative instrument output (e.g., chromatograms) and/or degradation information obtained from stress studies (e.g., results of peak purity experiments performed on degraded samples).

Experimental approach

The experimental protocol for degradation studies of new drug substances and drug products ideally will result in samples that either have been degraded 10% or have been exposed to an amount of energy that slightly exceeds that supplied under accelerated storage conditions (e.g., 40⁰C for 6 months).

Forced degradation studies should be conducted whenever a stability-indicating method is required. Studies may need to be repeated as methods, processes, or formulations change. Alternatively, methods can be developed with a mixture of the known degradation products, if available. Forced degradation studies should be performed on each unique formulation before formal stability studies begin.

Table I shows a general outline for degradation studies of new drug substances and drug products that was endorsed at the workshop. Sufficient exposure of a drug substance or drug product is achieved when the drug substance has degraded 10% from its initial amount or after an exposure in excess of the energy provided by accelerated storage (e.g., 40⁰C for 6 months), whichever comes first. Application of this rule of thumb may result in no degradation in some cases. The goal is to generate degradation in profile that mimics what would be observed in formal stability studies under ICH conditions.

The duration of storage required at a given temperature can be estimated by making conservative kinetic assumptions. The energy of activation, Ea, represents the quantitative relationship between reaction rate and temperature. The range of activation energies for most drug substances is 12–24 kcal/mole with an average of about 19–20 kcal/mole.

Assuming activation energy of 12 kcal/ mole affords nearly a doubling of the reaction rate for every 10⁰C increase in temperature. (Recognize that this is a conservative estimate and that activation energy of 20 kcal/mole affords about a 2.5- to 3-fold increase in reaction rate for every 10⁰C increase in temperature.) With this relationship, one can calculate the amount of time a sample should be stored at a specified temperature to achieve the energy equivalent of exposure at accelerated stability conditions (e.g., 40⁰C for 6 months). A sample of bulk drug substance stored at 80⁰C would be stored for 12 days. Thus, for a compound that degrades with Ea -12 kcal/mole, storage at 80⁰C for 12 days is kinetically equivalent to storage at 40 _C for 6 months.

Suggested equipment and exposure levels for photo stability stress testing are described in ICH and FDA guidance. Light storage should be in sufficient excess of ICH light conditions. The guidance states that solution-phase degradation studies of a drug substance can be carried out in solution or in suspension. The use of inert organic cosolvents may be indicated in cases in which drug substances are extremely insoluble but recognize the potential of any organic co solvent to react with the drug substance under a given set of stress conditions.

For drug products, non–drug substance related peaks should be distinguished from drug substance related compounds. This process can be accomplished through comparative analysis of stressed samples of drug substance alone, of drug substance plus excipients, and of excipients alone. Stressing drug substance and/or excipient blends instead of final dosage forms may be adequate for the determination of degradation pathways of a drug product. However, there may be significant differences in degradation profiles observed between blends and actual drug products. Consideration also should be given to the possibility of a reaction between the drug substance and components of a film-coating or capsule shell. For combination parenteral or aerosol products, the guidance recommends an investigation of the chemical compatibility or stability of multiple actives that will be combined before administration. By extension, any combination product should be stressed to examine for drug–drug interactions potentially manifested by accelerated degradation and/or new degradation pathways and products. Early investigation can facilitate development of an optimum formulation as well as stability-indicating methodology. Consideration may be given to stereochemical stability, mass balance, and crystal-form stability. Stereoisomers should be treated like any other potential degradation product. Failure to observe an increase in stereoisomers during forced degradation studies may be sufficient justification to eliminate testing for stereoisomers during stability studies.

Investigation of the mass balance in degraded samples can reveal the adequacy of the analytical methods to examine for degradation products. Assessing mass balance is the process of adding the assay value and levels of degradation products to see how closely these add to 100% of the initial value, with due consideration of the margin of analytical error. In cases in which substantial mass loss is observed, efforts to account for the missing mass should be made such as consideration of response factors or the formation of highly retained or volatile degradation products. FDA recognizes that mass balance may not be obtained in all cases and instead emphasizes the thoroughness of the investigation to determine the specificity of the assay and the pathways of degradation. The chemical and physical stability of crystal forms, if relevant, should be investigated. This analysis could include evaluation of stressed solid-state samples for changes in crystallinity or crystal form.

Method specificity for the active ingredient can be established by peak purity experiments using hyphenated techniques such as liquid chromatography (LC)–MS, LC–UV (photodiode array detection), and LC–NMR or orthogonal methods. If needed, degradation product structure elucidation can be accomplished with hyphenated techniques (e.g., LC–MS, LC–UV, and LC–NMR) or by synthesis and/or isolation. Structure elucidation may be postponed until the drug demonstrates safety and efficacy.

A decision to isolate and/or characterize a degradation product should be based primarily on results obtained from formal stability studies of the drug substance and drug product whenever possible. The guidance provides the identification thresholds for degradation products in drug substances and drug products found in formal stability studies.

Summary

Forced degradation studies of new drug substances and drug products are essential to help develop and demonstrate specificity of stability-indicating methods and to determine the degradation pathways and degradation products of the active ingredients.

They also can be useful in the investigation of the chemical and physical stability of crystal forms, the stereochemical stability of the drug substance alone and in the drug product and mass-balance issues, and for differentiating drug substance–related degradation products in formulations. Procedures for the preparation of specific degradation products needed for method validation often emerge from these studies. Knowledge gained from these studies can be used to guide formulation development and improve manufacturing and packaging processes.

For marketing applications, current FDA and ICH guidance recommends inclusion of the results, including chromatograms of stressed samples, demonstration of the stability-indicating nature of the analytical procedures, and the degradation pathways of the drug substance in solution, solid state, and drug product. The structures of significant degradation products and the associated procedures for their isolation and/or characterization also are expected to be included in the filing. The experimental protocol for degradation studies will depend on the active ingredients and formulation involved because the chemistry of each compound is different. A target of the lesser of 10% degradation of the active ingredient or exposure to energy in slight excess of accelerated storage is recommended. A compound may not necessarily degrade under a given stress condition. No further stressing is advised in these cases.

References

1. FDA, “International Conference on Harmonization: Stability Testing of New Drug Substances and Products,” Federal Register 59 (183), 48753–48759 (22 September 1994) (ICH Q1A).

2. FDA, “International Conference on Harmonization: Draft Revised Guidance on Q1A(R) Stability Testing of New Drug Substances and Products,” Federal Register 65 (78), 21446–21453 (21 April 2000) [ICH Q1A(R)]. This revised guideline reached Step 4 of the ICH process on 8 November 2000. Implementation as of this writing — EU: adopted by CPMP, November 2000, issued as CPMP/ICH/2736/99.MHW: to be notified. FDA: to be notified.

3. FDA,“Draft Guidance for Industry, Stability Testing of Drug Substances and Drug Products,” Federal Register (Notices) 63 (109), 31224–31225 (8 June 1998) (combination of ICH Q1A-Q1C and Q5C, draft).

4. FDA, “INDs for Phase II and III Studies of Drugs, Including Specified Therapeutic Biotechnology Derived Products,” Federal Register (Notices) 64 (76), 19543–19544 (21 April 1999).

5. FDA, Center for Drug Evaluation and Research, “Submitting Documentation for the Stability of Human Drugs and Biologics” (Rockville, MD, February 1987).

6. FDA, “International Conference on Harmonization: Guideline for the Photostability Testing of New Drug Substances and New Drug Products,” Federal Register 62 (95), 27115–27122 (16 May 1997) (ICH Q1B) and References 1 and 2.

7. FDA, “International Conference on Harmonization: Guideline on Impurities in New Drug Substances,” Federal Register (Notices) 61 (3), 371–376 (4 January 1996) (ICH Q3A) and FDA, “International Conference on Harmonization: Draft Revised Guidance on Impurities in New Drug Substances,” Federal Register (Notices) 65 (140), 45085– 45090 (20 July 2000) [ICH Q3A(R)]. ICH Q3A(R) currently is at Step 3.

8. FDA, “International Conference on Harmonization: Guideline on Impurities in New Drug Products,” Federal Register (Notices) 62 (96), 27453–274561 (19 May 1997) (ICH Q3B) and FDA, “International Conference on Harmonization: Draft Revised Guidance on Impurities in New Drug Products,” Federal Register (Notices) 65 (139), 44791–44797 (19 July 2000) [ICH Q3B(R)]. ICH Q3B(R) currently is at Step 3.

9. A,“Draft Guidance for Industry on Analytical Procedures and Methods Vaidation Chemistry, Manufacturing, and Controls Documentation,” Federal Register (Notices) 65 (169), 52776–52777 (30 August 2000).

10.FDA, “International Conference on Harmonization: Guideline on the Validation of Analytical Procedures: Methodology, Availability, Notice,” Federal Register 62 (96), 27463–27467 (19 May 1997).

11.A. Conners, G.L.Amidon, and V.L. Stella, Chemical Stability of Pharmaceuticals (Wiley and Sons, New York, New York, 2d Ed., 1986), p. 19 and Reference 3.

12 FDA,“International Conference on Harmonization: Guidance on Q6A Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances,” Federal Register (Notices) 65 (251), 83041–83063 (29 December 2000) (ICH Q6A) and FDA, “International Conference on Harmonization: Draft Guidance on Q6A Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances,” Federal Register (Notices) 62 (227), 62889–62910 (25 November 1997) (ICH Q6A). PT

FERTILITY ( GROWTH PROMOTION ) TEST FOR MEDIA.

2011-01-13T23:29:00.000-08:00

1.0 OBJECTIVE

To lay down the procedure for fertility ( growth promotion ) test for media.

2.0 RESPONSIBILTY

Microbiologist./ Q.C Executive

3.0 ACCOUNTABILITY

Head - Quality Control

4.0 PROCEDURE

4.1 Prepare media as per SOP No – K/QC/050

4.2 The selection of organisms depends on medium to be subjected to fertility test.

4.3 Subculture the required organism ( like: - S. aureus, C.albicans, , B. subtilis, C. sporogenes,E.coli , Salmonella and Pseudomonas ) on Nutrient agar slants ( for bacteria ) and Soyabean casein digest agar ( for fungi ) , one day before, to get 24 hrs old culture.

4.4 Prepare thin suspension and dilute it serially so as to get 10 - 100 cfu/ml which shall be determined by plate counts.

4.5 Keep the inoculated plates for incubation and serial dilution tubes in the refrigerator.

4.6 After confirmation of the counts, inoculate 1ml of suspension containing 10-100 cfu/ml into the media taken for growth promotion test and incubate them at the required temperatures ( i.e at 30 - 35°C for bacteria , 20-25°C for fungi ).

4.7 If the growth occurs within three days in case of bacteria and five days in case of fungus the media is found suitable for microbiological testing.

4.8 In case if the medium is not differential as in case of Tetrathionate broth , the subsequent tests, as per respective General procedure, shall be carried out to demonstrate the fertility of the medium

4.9 Record the details in the format mentioned in Annexure I

4.10 FREQUENCY

Every new batch or lot of dehydrated media.

4.2 MEDIA STOCK REOCRD

4.2.1 Take the stock of dehydrated media once in a six month.

4.2.2 Dehydrated media received from any supplies should be entered as per Annexure no II and similarly issued qty and remaining qty should be enter date wise in the mention above annexure.

4.3 ABBREVIATIONS

Cfu - Colony forming unit

Ml - Milliliter

5.0 REASON FOR REVISION

Change in format

6.0 TRAINING:

Trainer -- Head – Quality Control

Trainees-- Quality Control Chemists & Assistants

Period -- One day

7.0 DISTRIBUTION:

Certified Copy No. 1 : Head of Department – Quality Control

Original Copy : Head – QUALITY ASSURANCE.

8.0 ANNEXURES:

Annexure-I Format for fertility test of Media

Annexure- II Media Stock Record.

9.0 REFERENCES:

USP 25 Page no.-1879

ANNEXURE I

FERTILITY (GROWTH PROMOTION) TEST OF MEDIA

REF. SOP NO.:	Revision No. : 01	Page No.: 1 of 1
	Effective Date:

NAME OF MEDIA		DATE OF PREPARATION
BATCH NO.		STERILI. TEMP./ TIME
MAKE		STERILIZATION DONE BY
MFG. DATE		ORGANISM USED
EXP. DATE		DATE OF TEST

BRACKETING OF ORGANISM:

NAME OF ORGANISM	SERIAL DILUTIONS
NAME OF ORGANISM	1 : 10	1 : 100	1 : 1000	1 : 10000	1 : 100000

INCUBATION TEMPERATURE: Between to °C for bacteria

Between to °C for fungi

NAME OF ORGANISM	GROWTH OBSERVED
NAME OF ORGANISM	1 DAY	2 DAY	3 DAY	4 DAY	5 DAY



Observed By

Acceptance criteria: Bacteria must show clear colony forming units / turbidity within three days.

: Fungi must show clear colony forming units / turbidity within five days.

OBSERVATION : GROWTH OF MICRO-ORGANISMS IN THE FORM OF TURBIDITY /COLONY OBSERVED / NOT OBSERVED ON THE MEDIA .

RECOMMENDATION: MEDIA IS FOUND SUITABLE / NOT SUITABLE FOR PERFORMING MICROBIOLOGICAL TESTING

MICROBIOLOGIST CHECKED BY

SIGN & DATE SIGN & DATE

ANNEXURE II

MEDIA STOCK RECORD

REF. SOP NO.:	Revision No. : 01	Page No.: 1 of 1
	Effective Date:

NAME OF MEDIA : ______________________________________________ CODE NO:__________

Date of Receiving or Issued	Batch No.	Expiry Date	Fertility test status	Quantity received of Issued	Balance Quantity	Issued by

MICROBIOLOGIST CHECKED BY

SIGN & DATE SIGN & DATE

OPERATION AND CLEANING OF MOIST HEAT STERILIZER

2011-01-13T23:24:00.001-08:00

1.0 OBJECTIVE

To lay down a procedure for operation and cleaning of autoclave

2.0 RESPONSIBILTY

Microbiologist./ Q.C Executive

3.0 ACCOUNTABILITY

Head - Quality Control

4.0 PROCEDURE

4.1 : PRE-START UP

4.1.1 : Ensure the cleanliness of the room and machine.

4.1.2 : Ensure that all utilities such as pure steam, water, power etc are available.

4.1.3 : Check that material are ready for auto clave and Load the autoclave as per load pattern

given in Annexure-1 along with the necessary temperature indicators.

4.1.4 : Ensure AHU of area is working.

4.1.5 : Inside door of the autoclave is closed properly.

4.2 : START UP

4.2.1 : Open pure steam valve from service floor.

4.2.2 : Open main valve of steam line .

4.2.3 : Open steam by-pass valve for condense out let.

4.2.4 : Close steam by pass valve after completely out let of condensate

4.2.5 : Open main valve on steam line connecting to chamber.

4.2.6 : Open the valve before trap on steam line.

4.2.7 : Close the door of the autoclave tightly.

4.2.8 : ON machine by pressing green color OFF/ON switch on loading side panel to start the

sterilization cycle.

4.2.9 : Press the F1 button of the PLC of autoclave after getting auto mode indicated by a red

indicator.

4.2.10 : Press F3 for cycle selection , select the cycle and press enter. selection of auto mode.

4.2.11 : Then press start button

4.2.12 : Close the outlet of jacket and chamber steam.

4.2.13 : When the PLC of autoclave shows sterilization cycle complete switch off the autoclave

and open the outlet of chamber and steam.

4.2.14 : After each day of working clean ( by moping) the autoclave with disinfectant solution.

4.3 : SHUT DOWN.

4.3.1 : At the end of cycle, Unload the sterilized material from sterile side

4.3.2 : Check the change in steam clox indicator. It should change as per Manufacturer instructions.

4.3.3 : Attach steam-clox in media preparation record and note down operation.

5.0 : Cleaning :

5.1 : Pre checks.

5.1.1 : Ensure that loading door is open and door to sterile side is closed.

5.1.2 : Ensure that autoclave panel electrical supply cut off.

5.1.3 : Ensure that no material is present inside the autoclave.

5.1.4 : Ensure that outer surface of autoclave is cool and is at room temperature.

5.1.5 : Ensure that all utility supply links to the autoclave are closed.

5.2 : Daily cleaning : At the end of shift.

5.2.1 : Clean the utility inlet holes with a nylon brush and them mop with lint free cloth.

5.2.2 : Mope the chamber, probes, loading trolley & outer surface of autoclave with lint free

cloth dipped in purified water.

5.2.3 : Mope the autoclave chamber and loading trolley with water for injection.

5.2.4 : Wipe the chamber, probes, utility pendants and outer surface of the autoclave with lint

free cloth.

6.0 : Precaution :

6.1 : Jacket pressure should not be less than 1.2 kg per cm square.

7.0 : Abbreviations:

AHU = Air Handling Unit

Programmable Logic Control (PLC)

8.0 : Annexure : Annexure – 1 attached

9.0 : Reference : Instrument Manual

ANNEXURE I

Details of the abbreviations used in Schematic represented.

A - Media-Probe ,B.I and C.I. inside the media

B,C,Q,R,S-Media ,

D-Dress -Probe ,B.I and C.I. inside the Dress ,

E-Pippet Carrier ,

F- Pippet –Probe,B.I and C.I. inside the Carrier ,

G-Petri-Plate Carrier ,

H-Petri-Plate -Probe ,B.I and C.I. inside the Carrier ,

I-Petri-Plate Carrier ,

J-Petri-Plate -Probe ,B.I and C.I. inside the Carrier,

K-Petri-Plate Carrier ,

L-Manifold -Probe ,B.I and C.I. inside Filter Holder ,

M-Manifold Filter Holder ,

N-Liquid Media -Probe ,B.I and C.I. inside media

O-S-S Perforated Box With Filter Assembly

P-S-S Box With -Probe ,B.I and C.I. inside the Assembly , Filter Assembly

Preparation of Microbial Plates

2011-01-13T23:21:00.001-08:00

1.0 OBJECTIVE: The objective of this SOP is: to lay down a procedure for preparation of plates that can be used as settling plates and in various microbiological analysis.

2.0 RESPONSIBILITY

The Microbiologist shall be responsible for preparation of settle plates, their pre-incubation and related documentation.

3.0 ACCOUNTABILITY:

Executive - Quality Control

4.0 PROCEDURE:

4.1 Media with the content of agar can be used for the preparation of settle plates like.

i) Soyabean Casein Digest Agar (SCDA) - For enumerating Bacteria and Fungi (required for Environmental monitoring and Microbial limit tests.)

ii) Sabarauds Dextrose Agar (SDA) – For estimation of fungi.( Required for Microbial limit tests. )

4.2 Prepare media as per SOP.

4.3 Follow the gowning procedure and enter the M.L.T Room by following SOP.

4.4 Clean the LAF with 70% I.P.A and wait till drying.

4.5 Switch on LAF and UV lamp 15 min. before pouring the plates.

4.6 Open the containers containing sterile petri-dishes (That are previously sterilized by Autoclaving) and place on the working surface table of L.A.F.

4.7 Open the containers containing sterile petri-dishes and place them on the working table of LAF.

4.8 Take out the cotton plug of conical flask containing agar medium.

4.9 Sterilize the mouth of the conical flask by flaming it and start pouring about 20-25 ml of medium to each petri-dish quickly .

4.10 Cover the plates and keep under LAF, till they are solidified.

4.11 After getting solidified, preincubate the plates to the incubator at 30-35°C for 48 hrs to check any accidental contamination.

4.12 Check each and every plate under colony counter before exposure to the environment for monitoring.

4.13 Record the activity in Media preparation record.

5.0 TRAINING :

Trainer -- Executive – Quality Assurance

Trainees -- Microbiologists

Period -- One day

6.0 DISTRIBUTION:

Certified Copy No. 1 : Head of Department – Quality Control

Certified Copy No. 2 : Microbiology Department

Original Copy : Head – QUALITY ASSURANCE.

Disposing of microbiological culture media

2011-01-13T23:20:00.001-08:00

1.0 OBJECTIVE : To lay down a procedure for disposing of microbiological culture media.

2.0 RESPONSIBILTY

Microbiologist /Q. C Executive

3.0 ACCOUNTABILITY

Quality Control Manager

4.0 PROCEDURE

4.1 INTRODUCTION:

4.1.1 Bacteriological culture media contains all the nutritive sources which favors rapid growth of different types of Micro-organisms. Some selective media’s are used for cultivating specific type of Pathogenic organisms. The micro-organisms grown either on enriched or selective media’s if not disposed or destroyed in proper way can cause contamination of the environment which in turns is very hazardous.

4.2 METHOD:

4.2.1 Collect all the used semi solid media’s in plastic bag containing about 50 ml of 2.5% Savlon solution and close the opening tightly with a tag or rubber-band and transfer the it to the incinerator.

4.2.2 For liquid media add 2.5% disinfectant (savlon), to the liquid media ,mix it well ,hold for half an hour and then discard them in a stream of running tap water.

4.2.3 The plates & test tubes are then thoroughly washed with soap water and sterilized by autoclaving.

4.3 Procedure for cleaning of glass-wares

4.3.1 INTRODUCTION

Proper cleaning of glassware’s used in microbiology laboratory is very important in microbiological work. If the equipments used in microbiology are not cleaned properly, due to contamination, the microbiological results may get affected; also it can cause danger to the persons handling the equipment and risk of infection due to potential hazards of pathogenic cultures.

GMP require the standard procedure for glassware cleaning used in microbiological work. This procedure provides Guidelines for proper cleaning of glassware in micro section.

4.3.2 Method For Cleaning

4.3.2.1Keep all the glassware’s used in microbiology in the cupboard of the tables used by the Microbiologists to work.

4.3.2.2Do not use these glass wares in chemical testing.

4.3.2.3Rinse all the glass wares with tap water two to three times.

4.3.2.4Dip all the glass wares in 2% v/v solution (prepared in D.M water)of teepol or liquid soap for at least 4 hours, for depyrogenation dip it into 2.5% NaOH solution.

4.3.2.5Remove the glass wares from the solution.

4.3.2.6Rinse twice with D.M water followed by rinsing once with W.F.I

4.4 ABBREVIATIONS

W.F.I= Water For Injection, NaOH= Sodium hydroxide, %=Percentage, v/v =Volume by volume D.M water= De mineralized water

5.0 REASON FOR REVISION

Harmonization of format.

6.0 TRAINING:

Trainer -- Head – Quality Control

Trainees-- Quality Control Chemists & Assistants

Period -- One day

7.0 DISTRIBUTION:

Certified Copy No. 1 : Head of Department – Quality Control

Original Copy : Head – QUALITY ASSURANCE.