Changes in Regulatory and GMP Intelligence
by Barbara Unger, GMP Quality Expert and GMP Regulatory Intelligence Editor-in-Chief
Surveillance, analysis and communication of regulatory and GMP intelligence has evolved over the past decade. The individual(s) tasked with this activity within pharma companies require broad experience in regulatory affairs and GMP compliance. The individual(s) must have sufficient historical perspective to compare and contrast new requirements with those they replace and to compare requirements and expectations among the major health authorities. It is no longer sufficient to simply summarize new or revised requirements but rather it is necessary to provide the added value of determining how the new requirements may affect the firm’s operations.
Most large pharma companies now have dedicated staff for this activity covering all GXP areas. It is generally their responsibility to provide surveillance for new requirements and expectations and to effectively communicate this information to those in the company who are responsible to implement these requirements. These staff often provide guidance and insight into GXP enforcement trends which is frequently more challenging, and every bit as important as assessing changes in guidance documents or regulations.
Many features of GMP Intelligence and Regulatory Intelligence have remained the same over the years. Changes, or refinements, that directly impact regulatory and GMP intelligence programs in the past decade or so include, but are not limited to, the following six:
- GLOBALIZATION greatly expands the scope of countries that must be addressed in a GMP regulatory and GMP intelligence program. Firms have expanded both manufacturing activities and marketing into developing countries and those which are only beginning their development in the GXP regulatory areas. To monitor these areas optimally requires partnership with staff in the specific countries to interpret the intent of written requirements and enforcement activities. To be able to effectively compare and contrast the various requirements requires staff with deep expertise in GMP interpretation and application. This activity is challenging for firms that do not have affiliates in the global sites that may be important to them from a commercialization perspective.
Personally, one of the most significant challenges for the future is to obtain English translations of the many documents now published from the China FDA in both the drug and device area.
- TRANSPARENCY continues to increase in FDA activities and the scope and depth of data they make publicly available. The Europeans have recently started to release summary reports of GMP/GDP non-compliance. The specific details of objectionable findings are not provided in detail but general problem areas are identified. This is clearly a positive move for those of us who monitor enforcement activities. WHO publishes Notices of Concern for those inspections that show significant GXP deficiencies. The number of these reports is limited but their level of granularity and detail exceeds publications from the EU and is most similar to information in an FDA Establishment Inspection Report (EIR). Health Canada also publicly identifies those inspections where there is potential for significant impact to product quality and patient safety based on their own inspections and collaborations with other health authorities.
It would be ideal to have access to full EU and Health Canada inspection reports, though that does not seem to be likely anytime soon. It is, however, valuable that publication of these reports permit linkage among the inspections and enforcement activities of the major health authorities. I await additional public transparency of all inspection results in EC member states, Japan, Brazil, and China.
- SHARING AMONG REGULATORY AUTHORITIES has become more common and can often be tracked in their sequential GXP inspections and enforcement actions. Thus, when FDA issues a warning letter it’s useful to consider that other health authorities have received communications about the underlying inspection months before the warning letter publishes. Similarly, actions by European inspectorates including removal of GMP certificates, may prompt inspections and potential enforcement actions from FDA, WHO and others. No longer does a firm deal with one regulatory authority after a problematic inspection. Expect this communication among regulatory authorities to increase as all are attempting to effectively leverage limited resources. Regulatory and GMP intelligence staff must now track these related activities.
Sharing among global health authorities is another globalization effort that impacts the area of enforcement. A problematic inspection outcome from one authority often leads to inspections by several other regulatory authorities, and written communication from yet others. This also complicates business processes and potentially unnerves customers and business partners. A contract manufacturer, or a CRO against whom a health authority acts often suffers unfortunate consequences impacting the business of dozens of companies. Part of GMP Intelligence is to monitor these activities and communicate these to senior management.
- HARMONIZATION among health authorities is alive and well. The most recent examples include guidance published regarding data governance and data integrity from: FDA, EMA, WHO, PIC/S, and MHRA. While there are some differences among the guidances, they are quite similar and it seems to have helped that many of the same individuals contributed to the development of several of these. Let’s be optimistic that the same holds for other items in the future.
- Most ‘big pharma’ firms, and some of the larger generic drug firms, now have STAFF DEDICATED TO REGULATORY AND GMP INTELLIGENCE EFFORTS. This activity is no longer performed as a part-time effort and has become a more valued activity within the pharma organizations. Smaller and mid-sized firms, however, often do not have sufficient resources to devote to this effort.
- Surveillance of the many dozen websites where relevant information is published is more efficient with software developed to scan and highlight newly published information. SOFTWARE ASSISTED SURVEILLANCE allows more time for effective analysis and meaningful communication to the larger organization. The complication is that many large firms will often not permit uploading of such limited use software.
Regulatory and GMP Intelligence efforts continue to increase in importance and when done effectively it provides significant competitive advantages to pharmaceutical and device firms. Even the firms with dedicated staff rely on subscription based newsletters and publications to supplement their efforts. Often these publications cover the many trade group meetings where regulatory authorities provide insight into new or pending requirements. It is impractical to staff to attend all these meetings. It is essential for firms to remain aware of the shifts in interpretation of GMP requirements and expectations employing the many tools that are publicly available.
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