Dr. D would like to begin this week’s guidance with the wishing of a Big Happy 241st Birthday (November 10) to the United States Marine Corps (Semper Fi to my Marine Corps brothers and sisters), and a happy and peaceful Veteran’s Day (November 11) to all of those that have served this great nation honorably. I hope you find peace in knowing that it was the sacrifices made by you and your families that ensure America’s freedom and liberty will continue to prevail.

For this week’s guidance, Dr. D came across a seldom-cited Form 483 observation pertaining to organizational structure, or in the case of the establishment on the receiving end of this week’s warning letter, a lack of an acceptable structure. There is no question the medtech industry is a dynamic one, with acquisitions and divestitures occurring so frequently that sometimes stopping and asking, “Who’s on First” (Abbott and Costello fame) becomes a reasonable question. However, the FDA is also faced with the challenge of knowing “Who’s on First” when acquisitions and divestitures occur. For those of us that work in industry, it is up to us to ensure the device establishments we support have adequate resources allocated to ensure compliance with quality, regulatory and statutory requirements. This includes the creation of an adequate infrastructure. If during an inspection, the FDA investigator believes that an establishment has a deficient organizational structure, rest assured, a Form 483 observation will be forthcoming. Earn enough Form 483 observations during an inspection, fail to respond to the agency within 15 days, or provide a deficient response, and an agency warning letter will be in the offending establishment’s future. Remember, one of the more challenging tasks for Chief Jailable Officers (CJO) is attempting to mollify (look-it-up) the concerns of FDA investigators during their visits for that friendly cup of coffee and an inspection. However, if there are issues with the quality management system (QMS), placating (look-it-up) our dear friends from the agency may become an insurmountable task indeed. Enjoy

Warning Letter – November 3, 2016

As Dr. D mentioned, failing to have an adequate organizational structure is a seldom-cited issue. Most device establishments have enough industry experience to ensure that adequate quality and/or regulatory resources are available to support operations. If an establishment is resource challenged, there are always folks like Dr. D who can be quickly retained to fill gaps and work on specific projects such as scripting 510(k)’s or performing audits. However, integrating a new acquisition can present its own unique set of challenges, like getting newly acquired team members to play nicely in the same sandbox. Once the sand starts to fly, all bets are off. As mentioned in the warning letter awarded to this week’s offending establishment, attempts at integrating newly acquired products (and the organization) under the same QMS umbrella has not been successful and as a result, the compliance issue cited in a Form 483 observation. Equally as bad is a deficient response provided to FDA. The agency is usually pretty reasonable when presented with a timeline for achieving compliance. However, fail to accomplish the promised targets given to the agency and very bad things are on the regulatory horizon for a violative establishment. FYI, no crystal ball is needed to see the amount of regulatory pain the FDA is capable of unleashing.

Warning Letter Excerpt

Observation Five (5) “Failure to establish and maintain an adequate organizational structure to ensure that devices are designed and produced in accordance with the requirements of this part, as required by 21 CFR 820.20(b). Specifically, the organizational structure has not assured that acquired products are adequately integrated into your quality management system. The responsibility for reviewing and authorizing work performed under your quality management system has not assured that necessary activities have occurred prior to approving. For example, SPAG-2 and ONSET Mixing Pen products have not been adequately integrated into your Quality Management System (QMS) under design controls, production & process controls and corrective and preventative action (CAPA) controls. This is evidenced by the above violations pertaining to violations with design validation, corrective and preventative actions and nonconforming product evaluation, dispositioning and approval.”

“We reviewed your firm’s response and concluded that it is not adequate. We acknowledge you will develop a SOP detailing how to manage integrating purchased products/companies into your QMS and that you state this SOP will include developing change plans for acquisitions including phase reviews with senior level management with cross-functional departments to provide input into the change management process. We acknowledge that the SOP for how to manage integrating purchased products will be retrospectively applied to Valeant’s acquired products listed where Valeant Rochester is now the specification developer/owner. We acknowledge the Directive on Change Management 26.1-NDIR will be changed to require detailed change plans for acquired products and to define the functions that must provide input into the change process and that a gap assessment required and approved by quality leadership, at a minimum, will be required prior to product release under the Valeant QMS. However, these procedural changes have not been implemented to date and the retrospective review of purchase products has not been completed. Thus the adequacy of the response cannot be assessed.”

21 CFR, Part 820.20(b) – Management Responsibility

“(b) Organization. Each manufacturer shall establish and maintain an adequate organizational structure to ensure that devices are designed and produced in accordance with the requirements of this part.”

Compliance for Dummies

Identifying resources needed for supporting an adequate QMS is always a challenge, especially for small organizations. Can you say start-ups? Seriously, for mechanistic organizational structures, the typical layered quality organization tends to be the flavor of the day. There is a qualified quality manager and this individual is tasked with managing all aspects of the QMS, including product release. However, what happens if the quality organization is an organization of one or even less. Yes, Dr. D said less than one, such as a ½ Full Time Equivalent (FTE). Please do not laugh, it happens much more than you think. The same individual may be the quality and regulatory person in a five-person organization that relies heavily on their contract manufacturer and consultants. In fact, virtual companies are nothing new.

Regardless, the FDA demands that sufficient structure be in place to support the QMS. That being said, it is acceptable to outsource quality processes to contractors, providing that adequate controls are in place. For example, contractors need to be appropriately qualified and added to an establishment’s approved supplier’s List. The good news is that it is your establishment so you can script requirements for each contractor. If the establishment needs an auditor, then the expectation is that the auditor hired meets ISO 19011 requirements and has the appropriate experience. If the establishment needs a mechanical inspector, then the establishment should script requirements appropriate for mechanical inspection.

Additionally, each establishment should always have a published organizational chart. Now granted, most establishments are very protective of these org charts to prevent competitors from pillaging their organization. However, the FDA is going to demand to see one during an inspection. If an organizational chart has not been created or the chart fails to reflect quality in one more titles, a big red flag is raised. Remember, it is acceptable to list non-employees in an organization chart, especially if these contractors are filling critical quality roles.

Furthermore, when an acquisition or merger occurs, it is imperative that the establishment create a viable quality plan that covers all aspects of the integration process. The doctor cannot fathom attempting to integrate potentially disparate quality organizations under the same quality umbrella without the benefit of a plan. In fact, Dr. D knows that our friends from the agency would love to see quality plans when acquisitions and mergers result in the integration of new products into a new QMS: “Who’s on First?”

Takeaways

For this week’s guidance the doctor will leave the readers with just one takeaway. One: “Who’s on First?” Seriously, please do not be that organization that fails to successfully integrate new products and/or new team members into the QMS. Merging and integrating disparate quality cultures is always going to be a challenge. However, having a plan and executing to a plan will help establishments achieve integration success. Simply stated, a successful integration will hopefully equate to zero Form 48s observations when the FDA appears in the lobby for a cup of coffee and an inspection. In closing, thank you again for joining Dr. D, and I hope you found value in the guidance provided. Until the next installment of DG, cheers from Dr. D. and best wishes for continued professional success.

References

1. Code of Federal Regulation. (April 2015). Title 21 Part 820: Quality system regulation. Washington, D.C.: U.S. Government Printing Office.
2. Devine, C. (2011). Devine guidance for complying with the FDA’s quality system   regulation – 21 CFR, Part 820. Charleston, SC: Amazon.
3. Devine, C. (2013). Devine guidance for managing key attributes of a FDA-compliant quality management system – 21 CFR, Part 820 Compliance. Charleston, SC: Amazon.
4. FDA. (November 2016). Inspections, Compliance, Enforcement, and Criminal Investigations. Valeant Pharmaceuticals International. Accessed November 10, 2016. Retrieved from http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2016/ucm528043.htm