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The ramifications for a regulated company that is deemed to have obstructed a regulatory inspection can be extremely serious, as the consequences of products being deemed to be adulterated can result in it having no products to sell, and thus could very quickly go out of business.
In light this, it is of critical importance that a company should develop and establish appropriate policies and procedures for hosting regulatory inspections. Just as important is the need to train your staff in the company’s policies and procedures and their responsibilities during an inspection.
Avoiding Delaying an Inspection – Inspection Readiness
In order to avoid unreasonable delays in scheduling an inspection a company needs to performs its operations in a constant state of inspection readiness. This should include consistently performing your operations in compliance with all current Good Manufacturing or Laboratory Practices as appropriate.
In particular, it is important to continually assess your company’s compliance with regular self-audits in order to identify any deviations or deficiencies and promptly implement necessary corrective and preventative actions. Some reasonable explanations for delaying scheduling of an inspection are:
- The company does not manufacture on an on-going basis and the company requests a different date so that manufacturing will occur during the inspection.
- No manufacturing will be taking place during the proposed inspection period due to scheduled site maintenance
So that an inspection can proceed smoothly it is good practice to identify what the inspection is related to during the initial meeting and to seek to develop an agenda for the inspection. This will allow the appropriate members of staff to be available at the necessary times. However, delaying access to sterile areas until the inspector complies with the company’s gowning procedures is considered acceptable.
To avoid delays in providing documents and records for review it is critical that a company develops effective archival and retrieval systems. When an inspector requests documents for review they should be produced within thirty minutes if they are on-site and within twenty-four hours if the records are stored off-site.
This implies that when records are stored off-site it should be in a location which can be quickly accessed and the documents can be delivered to site within the required time scale.
Delays caused by:
- A need to translate documents into English
- The records are currently in use for manufacturing operations that are currently in progress
- A need to compile a large volume of documents
Are usually considered acceptable. However, excessive delays in producing requested documents may raise concerns about authenticity.
Avoiding Denying an Inspection – Responsibilities
In order to avoid allegations of denying an inspection it is critical that all staff have a clear understanding of their responsibilities. In particular, staff should be trained not to lie, mislead or deceive an inspector. Further, staff should only be allowed to answer questions which are within the responsibilities of their respective roles.
During an inspection, each inspector should be allocated a host who should accompany the inspector at all time while they are on-site. This will prevent the inspector having impromptu, unrecorded, conversations with members of staff. In addition, staff should be trained to be aware that anything they say which is heard by the inspector may be documented and could be taken out of context and present the inspector with a false impression.
In addition, the FDA may not accept as reasonable when certain key members of staff are not present. This shows that the expectation is that a company should have substitutes readily available to answer questions. The author is aware of a situation where arrangements were made for US based employees to provide computer support for an inspection taking in Europe.
Avoiding Limiting an Inspection
To avoid allegations of limiting access to relevant facilities, companies establish policies and procedures that clearly define which areas of a site are engaged in cGMP or cGLP activities and which areas of the site are not.
Any area, room, equipment or laboratory instrument that is not used for cGMP or cGLP activities should be clearly labelled as ‘Not for cGMP or cGLP Work’. In addition, any equipment or laboratory instrument that is not currently available for use, such as in the process of being installed, should be appropriately labelled.
Delaying access to sterile areas until the inspector complies with the company’s gowning procedures and complying with health and safety training requirements are considered acceptable.
As discussed the practice of taking photographs during an inspection is a controversial topic. The concerns for the company are that
- Trade secrets or proprietary information may be revelled
- Photography may breach confidentiality agreements with clients or customers
- The privacy rights of its staff, which are protected by data protection legislation, may be violated
In many jurisdictions any information, including photographs, collected during an inspection are regarded as confidential and protected from discloser by Official Secrets Acts or similar legislation. In the United States, however, any photographs taken during an inspection are releasable under the Freedom of Information Act.
Despite having no statutory right to take photographs or video tapes during a routine inspection. FDA inspectors have been given the directive to take photographs without the permission of the manufacturing company.
However, it is clear from the guidance document that the FDA will accept a reasonable explanation if a company wishes to limit the taking of photographs. The key criterion is the reasonableness of the company’s objection.
Therefore, the laboratory should:
- Have a written policy regarding the photography/videography ban in place prior to inspection, with an assertion that the reason for the policy is to comply with the laboratory’s legal obligations to its clients and/or protect client trade secret/business confidential information. This may result in the inspector exercising greater discretion when taking photographs.
- Place “NO PHOTOGRAPHY OR VIDEOGRAPHY” signs in the appropriate areas.
- Provide the inspector with the written policy at the start of the inspection.
- If, however, the inspector insists on taking photographs or making video or sound recordings and such photographs are taken, or video or sound recordings are made the laboratory should notify the regulatory agency, in writing, at the end of the inspection or as soon as possible afterwards, that the company asserts that the photographs contain trade secrets and/or confidential client or business information and the disclosure of which would cause competitive harm to the company and/or its clients. Although this would not prevent the regulatory agency from using photographic evidence in enforcement proceedings, it will place the agency on notice that the photographs should not be released to third parties.
During an inspection the inspector may request copies of records or data for later review. It is recommended that arrangements should be made for a member of staff to make copies of such documents for the inspector.
Such copies should be marked as an uncontrolled copy made for on each page and should be marked confidential. This will prevent the document from being released under a freedom of information request.
Avoiding Refusing to Permit Inspections
The behaviours that may constitute refusing to permit inspection are similar to those that constitute delaying or limiting inspections. Therefore, the comments in previous sections will also apply here.
It is, however, emphasised in order for an inspection can proceed in a smooth manner it is good practice to identify what the inspection is related to during the initial meeting and to seek to develop an agenda for the inspection.
This will allow the areas to be available when the inspector wishes to visit them. However, delaying access to sterile areas until the inspector complies with the company’s gowning procedures or delaying access to areas requiring specific health and safety training are considered acceptable.
Conclusions
There is no doubt that obstructing a regulatory inspection seriously undermines the entire inspection process and has the potential to compromise the quality of medicines reaching the public. It is also clear for a company that engages in such conduct can expect serious financial and business consequences.
In order to avoid being this situation a regulated company should develop and implement clear policies and procedures for hosting inspections by the regulatory authorities.
This should include:
- Identification of individuals who will host the inspection and those who may be required to provide input into the inspection
- A clear definition of which areas of a facility are performing regulated activities, and any areas, equipment or laboratory instruments that are not involved in cGMP or cGLP activities should be clearly signed
- A clear understanding of what documents an inspector can review
- An efficient system of document archival and retrieval that facilitates the rapid access to documents and records when required
- Training to ensure all staff understand roles and responsibilities during an inspection
However, perhaps the most important action a company can take is to be constantly operating in a state of inspection readiness.
References
- Guidance for Industry: Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug Inspection, FDA, Rockville, MD, 2014
- M. D. Smedley, Warning Letter WL: 320-13-21, FDA, Silver Spring, MD, 18 Jul 2013
- M. D. Smedley, Warning Letter WL: 320-13-20, FDA, Silver Spring, MD, 1 Jul 2013
- M. Dutcher, Warning Letter MIN 15 – 05, FDA, Minneapolis, MN, 30 Dec 2014
- T. J. Cosgrove, Warning Letter WL:320-16-06, FDA, Silver Spring, MD, 31 Dec 2015
