Inspections focus reviews

A further post-approval role for FDA concerns biennial facility inspections. These are performed by the Team Biologies, often in conjunction with a CMC reviewer from headquarters. Biennial inspections focus on maintenance of cGMPs during continued production post-approval and follow up on post-approval changes. Follow-up to the biennial inspections is coordinated by ORA with assistance from CDER s Office of Compliance (OC). Often, consultation from CDER s product divi-... 

Other areas of inspection focus include sampling protocols, in process controls and specifications, further guidance on the quality of data, computerised systems (more details will be given in the next section), and laboratory management to determine the overall GMP compliance of the facility. This latter area would include supervisory control and review and personnel qualifications and training. 

A form of inspection is the focus review that is conducted in conjunction with a comprehensive or verification review. This type of review is usually as result of a significant risk or hazard finding, an insurance/risk management project or an enforcement action by a regulatory agency. 

The purpose of a focus review is to concentrate on a particular process or audit component that requires a specialized team that is experienced in the category of focus required. For example, the focus review inspection of an electrical power generating plant required a team of millwrights, pipefitters, electricians, plumbers, and other trades when a property fire protection insurance visit was made to the plant. 

Specifications A specification describes actions using postconditions (perhaps drawn with state charts) the postconditions are written in terms of a vocabulary of objects and their static relationships, which is described in a type model. These documents must be inspected at external design reviews. Types, rather than classes, are the main focus. 

The justification associated with a refinement can be formal or informal it could even simply say, Joe said this will work. The verification techniques can be applied in varying degrees of rigor, from casual inspection to mathematical proof. In between, there is the more cost-effective option of making refinements the focus of design reviews and basing systematically defined test code on the specifications (see Figure 6.43). 

Plan data collection methods [Hint May choose from (1) inspection points, (2) focus groups, (3) monitoring for markers, (4) chart review, (5) observation, and (6) spontaneous report.]... 

There has been a major impact on the need for firms to be ready for the preapproval inspection (PAI) earlier than ever because of the increased number of FDA reviewers and the greatly reduced review times. Firms do not have the lag time that they had become accustomed to and typically used to focus on and prepare their facilities for inspection. Prior to PDUFA, the industry was accustomed to submitting its applications and subsequently having a long lead time before FDA initiated the pre-approval inspection. Lack of planning results in lengthy FDA-483 at the PAI because firms are simply not ready for the inspection at the time of the submission of the marketing application. 

This chapter will focus on some, but not all, of the areas in which the U.S. Food and Drug Administration (FDA) and the European Union (EU) regulatory authorities have attempted to coordinate their efforts to provide uniform rules and standards for the pharmaceutical industry. Specifically, we will review the efforts to harmonize approaches relating to inspections (including public disclosure of confidential information) and product approval or authorization (including clinical trials). While space limitations do not provide sufficient opportunity to describe each regulatory authority s system or the harmonization attempts in detail, it is our hope to provide some background of where the efforts are now, where the efforts are intended to go, and what we believe will be the results of these efforts. In addition, the author is much more familiar with the U.S. system than the EU system because of his experience and daily exposure with FDA, this chapter will focus more on the U.S. structure. 

Self-inspections, also known as internal andits, are a fnndamental activity of competent qnality assnrance. They typically focus on reviewing validation documents and the SOPs used to generate them. Gnidance is not nsnally audited unless it is effectively being used as the procedure for work. 

Three of the Warning Letters referred to a wider organizational review of electronic record/signature requirements beyond the scope of the particular computer systems that were the focus of the original inspection. Pharmaceutical and healthcare companies should ensure that they have a compliance plan that covers the whole part of their organization subject to 21 CFR Part 11. 

Suppliers should conduct SCRs on all critical software modules in order to capture deviations from programming standards, identify logic errors, and ensure software modularity. Tailored software developed to satisfy user requirements not catered for within the standard product offering should be a particular focus of attention as the risk of software failure increases for new software developments. SCRs should be documented in order to record observations raised against the software and resultant corrective actions. Further, documented evidence of the implementation of corrective actions should be available for inspection. Where software modules present a major risk to GxP compliance or evidence of internal SCRs is limited, the pharmaceutical organization should consider additional independent reviews. Table 31.12 details the scope and content of programming standards. 

The vulnerability assessment is an organized review of validation-related vulnerabilities concerning the facility. The above objective is best achieved by an organizational multidisciplinary task force. The internal audits and past 483s should be reviewed. The existing validation documentation should focus, in addition, on the inspection of the physical facility and critical equipment. 

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