Control of Quality Records in the Pharmaceutical Industry

Sunday, January 3, 2010

By : Jean White
Pharmaceutical Technology Europe

As in so many disciplines, the theory is much easier to accept than the practice. Before the task of maintaining document security becomes too overwhelming or shamefully neglected, it is prudent - and will save time and later frustration - to look at the number and nature of records involved. For the pharmaceutical industry (and companies embarking on ISO9000:2000 quality system development), all documents included in the processes of contract management, statutes, regulation, jurisdiction, purchasing (approved supplier records), receiving and shipping, design and development, production and administration (where applicable) are classed as "quality records" and "critical." The documents involved in the needs of any other interested parties (particularly customers) should also be considered.

The control and security of documents is more manageable if distribution is limited to those who "need to know." This means setting out the criteria for distribution at a very early stage in design and production development. Hard copy and electronic documents must be available for use where and when they are most needed. Every aspect of development and production, and the people involved in the process, must be considered carefully to ensure that everyone has the information they need, when they need it.

Creating a master document list
The main task will be to create a master document list that will record, in hard copy or electronically, all the documents involved - from contract review to final delivery of the product. The following questions must be asked at the first contract review stage:

- Is the document critical or non-critical?
- Who will control the list? (Preferably limited to one authorized individual.)
- Who will have authorized access for review, revision and amendment? (Usually the quality assurance manager, but in larger companies it could be the technical library staff or engineering staff.)
- Who should be considered when compiling the list of "authorized, responsible individuals"? Any persons responsible for review and release must be identified and their names and responsibilities circulated to other listed authorities. Keep a "signatories list" to safeguard against, and identify, the squiggles that some people use as signatures.
- Have the documents been subjected to the severest scrutiny before issue? Verification of content, a logical sequence of events with the reader in mind, grammar and spelling (particularly for international markets) should all be addressed.
- Are the documents clearly written with the reader in mind?
- Where do the documents begin to appear in the design and production process?
- Do they include user documents?
- What is the distribution? (Please, no uncontrolled copies!)
- What are the intradepartmental connections for each document and how are other agencies involved?
- Where will the documents be kept? (Secure from damage or other deterioration such as climate.)
- Who will be in charge of the documents at the point of use?
- Has documentation development been included in the quality plan and management quality objectives?

User publications are sometimes given short shrift in the development plans. Given their rightful place in the development process, questions will be asked such as: does the author need to know the product? At which stage should the author(s) be brought into the process? The answer is, the earlier the better: in fact, as soon as the design process is under way or even at the design note stage.

You may be under the impression that the above concerns are known and understood by all senior company executives, who govern themselves accordingly; unfortunately, they do not. I have seen files of critical documents stored in the most lamentable conditions, subject to the onslaught of seagulls. This is less likely to happen nowadays, with documents stored electronically. Many companies, however, simply update documents and put the latest version online at prescribed (or ad hoc) intervals, consigning previous versions to the waste basket. In some circumstances, the history and revision trail of the document can be preserved if the previous revisions have been exported to another authorized individual within the company, but this process can weaken the security of documents.

Password protection Given the many constraints surrounding the protection of our documents, many of us place great trust in our passwords. Unfortunately, as Steve Hughes, managing director of DLP Consulting, points out: "The flaws existing in current password application could lead to serious breaches of security. You can bypass password dialogue boxes in older Windows operating systems (pre-Win2000/XP)." He observes further that: "Although safeguards are available that include software for fingerprint recognition, encoding and encrypting documents, encoding and encrypting e-mail when it constitutes a part of the quality system, many files are not password-protected at document level. Time- and date-stamping on database records (for example, financial and testing records) could protect documents from unauthorized interference."

Legal implications In addition to the strictures expressed in the US Food and Drug Administration (FDA) standards, the legal implication of electronic data transfer has become a thorny issue. Publications such as The Legal Admissibility and Evidential Weight of Information Stored Electronically (BSI), although informative, simply add to our fears that we are becoming more and more embroiled in unmanageable requirements.

Best practice The remedy is to follow best practice wherever possible. This does make sense when you think of the pharmaceutical industry as being (like the aerospace industry) an unforgiving environment for error and where traceability is a critical factor in design and product development. The same security procedures that are used in the financial systems controlling life assurance, pensions and banking can apply, where the recording of transaction dates and times are vital and bespoke systems are built to ensure this protection. You can also

- protect the backup tape (make sure it doesn't fall into the wrong hands)
- lock the server room
- install a firewall to stop Internet hacking
- pay attention to LAN security
- have a procedure for signing off and make sure everyone follows it
- vet staff before assigning passwords and other authorization to them

As well as all the above precautions, I would like to think that you are paying close attention to the style and content of the documents. Clarity is essential; try to stay away from "management speak" and other faddy language that can clutter the best thought-out and well-intentioned policies and procedures.

The main thing is to start the document control process in small, manageable pieces. You can create categories for the master document list from components of standards such as ISO9000:2000, which cover every aspect of a quality system. This will ensure that you have included all possible document sources.

Remember to assign the relevant authorities and responsibilities at the earliest possible stage in the project. Nothing will create more confusion than a last minute attempt to assess and categorize documents. Document control is the number one cause of failure in assessment for ISO9000:2000, and the component which, if neglected, will cause the greatest difficulties. You don't want this to happen in your company, do you?

Comparative Evaluation of Three Active Air Samplers for the Monitoring of Airborne Microorganisms

By : Evelyn F.Der, Joe P. Stablein, Daniel A.Coleman,

The evaluation of airborne microorganisms is critical in the biopharmaceutical industry. For manufacturers that produce drugs in an aseptic environment, cleanrooms must meet strict standards. Regulatory requirements such as the US Food and Drug Administration’s Guidance for Industry, Sterile Drug Products Produced by Aseptic Processing: Current Good Manufacturing Practice and internal corporate policies require monitoring to verify that these standards are maintained. Cleanroom monitoring is dependent upon reliable instruments that are suitable for sampling airborne contaminants in an aseptic environment. These instruments must also be calibratable, portable, and easy to use. In this study, three active air samplers were evaluated for the collection of culturable airborne microorganisms. Bioaerosol collection includes whole microorganisms as well as fragments, toxins, and particulate waste products from all varieties of living things (1).

Materials and methods Air samplers.

The following air samplers were studied: • The “SAS Super 180” sampler (Bioscience International, Rockville, MD) aspirates air at 180 L/min through a solid 304 stainless steel sampling head with 219 precision-drilled holes positioned over the agar at a prescribed distance. After impaction, air exits through an exhaust screen. The unit can accommodate either a standard 55/84-mm contact plate or a 90-mm standard Petri dish below the sampling head. The sampler is fully programmable for features such as time between aspirations, volume of air for each aspiration, and total air volume to be sampled.

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Laboratory Equipment Qualification

The main goal in qualifying laboratory equipment is to ensure the validity of data.The current equipment qualification programs and procedures used within the pharmaceutical industry are based o­n regulatory requirements, voluntary standards, vendor practices, and industry practices.The result is considerable variation in the way pharmaceutical companies approach the qualification of laboratory equipment and the way they interpret the often vague requirements.The authors summarize the conclusions of the PhRMA Workshop o­n Acceptable Analytical Practices for the topic “Qualification of Laboratory Equipment.” They describe the areas ofagreement and offer options for areas in which there is variation o­n what is appropriate.

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Author(s):
Kenneth W. Sigvardson, Joseph A. Manalo,Robert W. Roller, Fatieh Saless, and David Wasserman.

Why FDA Compliance Helps

Thursday, December 31, 2009

By : Mark Andrew Woodcock

FDA Compliance is an integral part of manufacture in the food, drug and cosmetic industries, to ensure that the public is not put at risk from consuming or using any new or sustained products on the market. There are several aspects of compliance including Good Manufacturing Practise, packaging and labelling, marketing and other factors. As an agency of the Department of Health and Human Services, the FDA is enabled to issue laws and enforce these on the 95,000 regulated businesses under its authority. The FDA ensures regulatory compliance across a number of products including food (excluding red meat and poultry), drugs, medical devices, blood, biological products, and cosmetics. The sole aim of FDA compliance is to safeguard the health of consumers and maintain the quality of products.

Only when organizations integrate FDA Compliance into their working lifestyle instead of viewing it as simply another regulation, will the authorities, businesses and consumers be happy.

There are two major impacts that failure to comply can have; public injury and company prosecution. When a product is contaminated, packaged incorrectly or fails to meet any of the regulations, consumers are put at risk, their health may suffer and in extreme cases, this can result in death. If the ingredients listed on packaging is incorrect, allergic reactions are possible, just as when the strengths are confused accidental overdoses may occur. For companies who fail to comply with the FDA, there are several possible outcomes, all of which are harmful to the longevity of the business. Product recall and seizure not only damages profits, but it also damages the stock of the business, making it less attractive to trade with and buyers are less likely to purchase products off them. For serious defiance of FDA compliance, a business can be fined huge sums of money and individual employees can be subject to criminal prosecution and jail sentences if they are found to have put human life at risk. The FDA publishes a list of companies and individuals who have been barred from working in any of the industries covered by the FDA due to criminal and life threatening activities. This alone should put compliance at the top of an organisation's agenda.

Whilst many businesses see compliance and regulation as a hindrance to their productivity and effectiveness, the FDA is working to make its regulations easier for manufacturers to adhere to and less like a drain on resources and employee focus. Many of the regulations are open ended and general which allows managers to implement them to suit their individual business. Smaller organisations will require a different approach than larger companies and the open-endedness reflects this.

FDA Compliance covers record keeping, personnel qualifications, sanitation, cleanliness, equipment verification, process validation and complaint handling. All of these features work towards public satisfaction and safety, keeping the quality of food, drugs, cosmetics and other products under FDA regulation high, whilst allowing businesses to work in ways which suit them. There would be no point in enforcing all of these regulations if productivity was hampered and research stifled. These regulations still allow for advances in science and technology, but they put public safety as their top priority.

Creating a Master Validation Plan

By : Sami Power

You might be wondering what master validation plan is and how to create one for your organization. This article can help you understanding the principle of master validation plan and what is involved in creating one.

If you are in pharmaceutical business you have already noticed that you need a validation plan for qualifying your equipments, processes, cleaning systems, buildings and facilities. It is a regulatory requirement for you to create one and implement in your site. If you are to make your product safe, pure, effective and identifiable at all times for human use, you definitely need to create an effective MVP.

An effort to define master validation plan (MVP):
MVP is a strategic document which identifies the elements to be validated, the approach to be taken for validation of each element, the organizational responsibilities and the documentation to be produced in order to ensure full consideration is given to product quality aspects. It will show how the separate validation activities are organized and inter-linked. Overall it provides the details and relative timescales for the validation work to be performed.

You have to create standard operating procedures for the preparation of validation documents which are approved by the Quality Assurance.

When does a MVP required:
A MVP is needed when significant changes are made to the facilities, the equipment and processes which may affect the quality of the product. A risk assessment approach should be used to determine the scope and extent of validation. The MVP should be available prior to starting any of the validation activities

What should a MVP contains?
Each MVP shall describe the scope of the activities and address relevant key elements of validation affected by the change, indicating the actions and documents that will be needed. The key elements are those factors that can have an effect on product quality.

The content of the MVP should reflect the complexity of the extent of the validation activities to be undertaken. At minimum the MVP should address the following:

1. Title, statement of commitment and approval page.
2. Summary description of the project and its scope.
3. A statement of validation policy and the objectives of the validation activity
4. References to other existing validation documents.
5. A description of the organization and responsibilities for validation
6. The validation strategy to be adopted opposite Facilities and Systems (process equipment and services including automated systems), Materials, Quality Control, Personnel including training.
7. The intent in respect of Process Validation and Cleaning Validation for each of the drug product range.
8. The documentation management and control system to be used.
9. A description of the validation change management process.
10. An indicative relative timescale plan.
11. Clear acceptance criteria against which the outcome of the validation exercise will be judged.

Reporting requirement for master validation plan:
Each MVP should result in a report confirming that all validation activities have been completed satisfactorily.

It is recommended that a Summary Validation Report (or Master Validation Report) is prepared which summarizes activities undertaken, presents the overall conclusions and provides cross references to any associated reports or follow up actions.