REGULATORY EXPECTATIONS

Since 1982, a number of guidelines applicable to information technology (IT) and network applications have appeared for the validation of computer systems. Between 1995 and 1998, five comprehensive regulations and guidelines were published. It is therefore timely to compare these guidelines in regard to their scope and contents. 

This chapter reviews the regulations and guidelines that 

Title of Regulation/Guideline Country/ Field Authors/Source Regulatory Authority (RA)/ Pharmaceutical Industry (PI)/ Binding for the Industry (Y/N) Year of Publication 

Compliance Policy Guides on Computerized Drug Processing USA GMP FDA RA(Y) 1982-1987 

Guide to Inspection of Computerized Systems in Drug Processing ( Blue Book ) Reference Materials and Training Hids for Investigators USA GMP FDA RA(N) 1983 

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Risk is not minimized because applications are vendor supplied. The level of understanding and incorporation of regulatory expectations varies among vendors. An assessment of the vendor s quality practices should be conducted. 

It is expected that different companies will develop different levels of process understanding and the level of understanding for a particular product can increase over time (life cycle). These differences will need to be accommodated in regulatory policies through a clear articulation of what is a minimum regulatory expectation (e.g., current requirements of CMC review information and process validation) and what is an optional opportunity for companies to improve efficiency while reducing risk to quality and regulatory concerns. 

Each process owner is required to work closely with his or her QA counterpart. This ensures design and operational issues are clearly reviewed and approved by a representative from the quality assurance function, a regulatory expectation. The quality assurance counterpart must be familiar with the process, understand documentation supporting the process, and able to convey what approval the Quality... 

Current Regulatory Expectations for Microbial Bioburden Control during Nonsterile Manufacturing... 

CURRENT REGULATORY EXPECTATIONS FOR MICROBIAL BIOBURDEN CONTROL DURING NONSTERILE MANUFACTURING... 

Regulatory expectations for microbial bioburden for nonsterile pharmaceutical products are reviewed using the FDA guide to inspections of microbiological quality control laboratories [2], purified water systems [27], topical products [28], and oral solutions and suspensions [29]. 

The environment in which this method is used changes significantly when the method is transferred to a quality control laboratory. The method may be replicated in several laboratories, multiple analysts may use it, the method may be one of many methods used in the laboratory, and the technical depth of the analysts may be less deep than those in the development laboratory. Thus, it is incumbent on the development laboratory to recognize when projects move to later phases of development. The developing laboratory must be aware of the needs of the receiving laboratories as well as regulatory expectations for... 

In summary, a successfully executed qualification of a stability chamber will ensure that the chamber will perform within its intended range of operation and that stability studies are performed at the proper storage condition within specified tolerance limits and according to current regulatory expectations. 

In fact, it is a regulatory expectation that an appropriate excipient be chosen and its level (amount) in a formulation be demonstrated and justified through formulation screening and development studies (29,30). The science of protein formulation development has become increasingly sophisticated over the past 20 years and its discussion is beyond the scope of this chapter. The interested reader is referred to excellent reviews on this subject for further study (31-34). 

After visiting and inspecting the supplier, the information obtained is analyzed against the acceptance criteria, current company requirements for the validation of computer systems, and the regulatory expectations for computing environments. A report is produced that documents the audit process, provides information on the current state of validation of the supplier and what may be needed for compliance and, based on the audit findings, provides a recommendation on whether the supplier can be used. 

In business terms, auditing of software developers will allow you to assess the vendor s technical competence, vendor reaction to your company s user requirements specification (URS), vendor QA system adequacy, supplier experience with GXP systems, and quality level of vendor-prepared validation and qualification protocols. In short, vendor auditing is a regulatory expectation and auditing provides a means of assessing the supplier s ability to deliver a validatable system that will achieve the requirements of your company s URS. 

In compliance terms effective change management and change control are a clear regulatory expectation. 

Simply stated, vendor qualification is the combination of activities required to ensure that a vendor will meet the professional and regulatory expectations of the sponsor. 

Provide a benchmark of compliance with other companies and regulatory expectations. 

The staff is comfortable with just meeting the minimum regulatory expectations. 

Identifies, installs, and maintains quality standards exceeding regulatory expectations... 

Many companies are only prepared to meet regulatory expectations and provide the minimum requirements. The goal of assessment is not to appease the regulatory agencies but to build quality into the various systems, identify deficiencies early on, identify the genesis of system failures, and ensure continuous improvement. There are myriad resources available from which information can be captured and utilized to assist with the benchmarking initiative. 

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