For years, drug companies that manufactured 
and sold their products in the United States
used internally developed spreadsheets
to monitor and analyze quality data, internal audits,
complaints and CAPA.
Today companies are global. Their manufacturing operations
and customers are located all over the world.
Spreadsheets are no longer viable.
To ensure that products are safe and effective, government agencies
oversee the process of drug development and manufacturing. In the
United States, drug companies are most concerned with the Food and
Drug Administration. To obtain the FDA inspection classification of
“No Action Indicated” or “Voluntary Action Indicated,” companies
must prove they are operating in a state of control.
To do this, they need to:
- Have written standard operating procedures that
show how the firm will comply with the requirements, - Follow those procedures,
- Document that they followed the procedures, and
- Produce the records in a timely manner in response to
a request by an FDA investigator during an inspection.
Many companies have multiple plants in which the employees have developed systems internally. Frequently these systems are unable to share data among the operating divisions. When an FDA investigator asks for documentation, an employee at an individual plant may be challenged to provide the documentation demonstrating that the entire company is operating in a state of control.
To respond to this challenge, many companies are using Enterprise Quality Management Software (EQMS). This software creates a Web-based workflow process that employees can use to document their compliance with FDA’s regulatory requirements. When an FDA investigator requests records, the designated employee can access the data and produce the reports in minutes rather than hours or days.
Today, more than ever, FDA expects drug firms to be efficient and expeditiously provide an investigator with records that demonstrate the firm’s regulatory compliance.
In July 2013, FDA published a draft guidance titled, “Industry Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug Inspection.”
The purpose of the draft guidance was to fulfill a congressional mandate in the Food and Drug Administration Safety and Innovation Act passed in 2012. The law states that within one year from passage, FDA would have to provide guidance as to the circumstances that would constitute delaying, denying, limiting or refusing a drug inspection. The penalty for firms
engaging in one or more of the behaviors listed above is that a firm’s drug would be considered to be adulterated under Section 505(j) of the Federal Food, Drug, and Cosmetic Act (FDC Act).
The draft guidance says that firms are required to cooperate with the FDA investigator when he/she conducts the inspection. FDA expects personnel at drug firms to:
- Facilitate rather than obstruct the scheduling of the inspection,
- Allow the investigator access to areas that he/she is entitled to see and to photograph,
- Be truthful and not attempt to mislead the investigator,
- Produce records in a timely manner.
Although the draft guidance appears to articulate normal conduct by any law abiding drug firm, it fails to define key terms.
Under the section titled “Delay Producing Records,” the draft guidance states “Examples of delays in producing records that may cause a drug to be adulterated… include… During an inspection, the FDA investigator requests records FDA has authority to inspect within a specific, reasonable timeframe, but the facility fails to produce the requested records within the timeframe requested by FDA, without adequate justification.”
Specific terminology used in the draft guidance is not defined and will be subject to the interpretation of the reader. What would personnel in FDA headquarters deem to be:
A “specific, reasonable timeframe” to produce records or
“Adequate justification” for not producing the records in that timeframe?
Without more specificity, would the definition by the personnel in FDA headquarters concur with the perception of the numerous FDA investigators located all over the world who are conducting inspections of drug facilities?
In a July 18, 2013 warning letter addressed to Wockhardt Limited, FDA cited the firm for taking two days to provide records the FDA investigator requested. The investigator asked for the records on March 20, 2013, and the firm provided them at the closeout meeting on March 22, 2013. (The warning letter says that the FDA investigator had asked the firm for the records on numerous occasions during the two day period.) The penalty for this and other activities was that FDA considered Wocklhardt’s drugs to be adulterated under 505(j) of the FDC Act.
Although the guidance is now in draft, the July 18 warning letter demonstrates that FDA currently is enforcing the law.
The judgment of what is a “reasonable timeframe” for producing records or what is “adequate justification” for not producing the records is being left to each investigator, at least for the time being. To be responsive, companies must have organized systems with checks to ensure that employees are adhering to the requirements for documentation.
In a manual system, mistakes often occur. Records are not filled out completely, or they may not be able to be located quickly when the FDA investigator asks for them. Companies who have
EQMS systems have checks in place to ensure that employees input the necessary information and can locate the records quickly.
In a bench marking survey conducted by my firm, Compliance-Alliance, on CAPA, a number of the pharmaceutical company respondents indicated that they are using an EQMS system like TrackWise from Sparta Systems. Many of these EQMS systems have CAPA processes that are configurable, easy to use, and efficient, as all of the records related to an incident are located in one place and reports can be generated by all authorized personnel. In addition, EQMS systems may be configured for audits, adverse event reporting, change control, complaints, deviations, supplier quality management and training.
Today all drug firms should use EQMS. This will enable them to produce complete records in minutes and eliminate the threat of receiving a warning letter for having an adulterated drug because of delaying an inspection.
About the Author:
Nancy Singer writes on behalf of Sparta Systems and founded Compliance-Alliance, LLC to specialize in the professional development for FDA and industry employees. In her role as Special Counsel, Nancy was a member of the FDA/industry working group that evaluated and suggested reforms to the FDA inspectional process. Nancy began her career as an attorney with the United States Department of Justice where she did litigation for the Food and Drug Administration. Subsequently she was a partner at the law firm of Kleinfeld, Kaplan and Becker.