Compliant Operations
A Lean Approach to Meeting Internal and External Regulatory Requirements
by Patrick Lucansky, Larissa Potapchuk, Robert Burke and Ed Pokropski
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Is 'Lean Compliance' an oxymoron, or is it compliance at any cost? Can an organization be lean and compliant without compromising quality and customer service? Many life sciences organizations are wrestling with these dilemmas as profit margins get squeezed and regulatory bodies stiffen compliance requirements (see inset 1…the FDA warning system). A common misconception is the statement, “that Lean thing won’t work in our industry especially where the FDA is concerned.” It is our contention that life sciences' firms can maintain compliance, quality and customer service while operating in a Lean environment where meeting customer needs (both regulatory and end-user) is the primary goal. The objective is to take Lean thinking into your regulated environment to improve service, quality and cost performance, in parallel with ensuring and improving compliance performance.
Compliance Impacts Broader Business PerformanceMany organizations are challenged with pressing, mission critical requirements administered by legislation to conform to external regulatory requirements. Consistent non-compliance can ultimately result in imposed business closure and unnecessary shareholder losses. In a regulated environment compliance is essential. For example, the time and cost of bringing a new drug to market, 15 years and $500 million, combined with any type of delay puts pressure on an organization to find ways to reduce costs, take shortcuts and possibly end up non compliant in a rush to market. The delay of a drug to market can cost a pharmaceutical company millions of dollars per day and in a worst-case scenario can threaten the lives of patients and the existence of the organization.
While most life sciences organizations are dedicated to providing quality, altruistic products to enhance and extend the quality of our lives, they generally do so at a great cost to themselves and to consumers |
This is a greater concern during this time of increased political and public scrutiny on product costs. Internally, we find functional departments (regulatory, compliance, quality control and quality assurance) competing for control and ownership without focus on business effectiveness. The internal organizational structure often times further confuses the situation with unclear lines of communication and reporting. Some companies believe the answer lies in more or better technology such as faster processing equipment, new IT systems or new software.
Furthermore, this problem is compounded by the desire for the next block-buster drug and pressure from investors to produce returns and increase profit margins. These challenges drive companies to treat symptoms instead of finding and solving the root cause…or compliance at any cost thinking. For example, we have seen many drug safety departments when confronted with regulatory body warnings for non-compliance (see inset 2 on Safety Reporting for Post Marketed Drugs) historically install two fixes: quality gates (additional quality checks or reviews) and doubling or tripling of staff which when reviewed have shown to be unsuccessful at catching errors (one company we interviewed had 2 quality gates in its process and still had 25% of the paperwork going to the FDA wrong). The quality gates are set in place to catch the errors and 'inspect in' quality, while the extra personnel is needed to staff these policing activities. These vast, extensive, over-engineered internal systems are obviously costly and quite often provide little to no additional value. Additionally, they create a throw it over the wall attitude (the next person will find any error missed because this type of system does not create an attitude of right first time.) What happens when the department workload (AE Processing) doubles or triples? Can these systems do the same (i.e. can these systems handle this increased volume)?…we think not. |
FDA Surveillance and Warning Process
The value of adhering to regulatory compliance is immeasurable for an effective relationship with the FDA and for profitable business management. One way that regulatory compliance is assessed is through operational reviews and inspections of manufacturing facilities. The FDA will continue to enforce the rules and regulations requiring companies to carefully control and monitor their processes used to make pharmaceuticals and other products, so that those products will be safe and effective for consumers. If corrective action is not implemented after numerous citing’s for compliance violations, the FDA may take legal action to prevent the manufacturer from continuing operations. The process starts with a scheduled inspection of the manufacturer's facility and may end with an order to cease operations, if compliance to regulations is not demonstrated. The process for this Surveillance is stated below.
Inspection
FDA Inspectors conduct a review or inspection of the manufacturer's operations to ensure that the operations are in compliance with regulatory requirements cGMPs - current Good Manufacturing Procedures]. Findings are discussed with representatives of the manufacturer. At this time, these representatives can address concerns of the Inspectors.
Warning Letter (FDA 483)
The FDA process for formally presenting areas of non-compliance after a review or inspection is through the Warning Letter. Inspector findings are documented in a Letter to the manufacturer [FDA- 483] which describes the Inspector's findings in areas of noncompliance.
Response to Letter
The manufacturer may respond to the Letter identifying the plan to address the findings and submit corrective action plans to remedy the deficiencies. A schedule to implement the corrective actions may be included.
Review or Inspection
The FDA will conduct follow-up inspections to ensure that the non-compliant issues have been addressed and corrected. Numerous attempts to ensure that the manufacturer is operating under cGMPs will be conducted, with the FDA issuing Warning Letters and conducting follow-up inspections.
Compliant for Injunction
After corrective actions for non-compliant items have not been implemented and the same violations have been identified after continued inspections, the FDA may seek a Complaint for Injunction against the manufacturer.
Consent Decree
A Consent Decree can be issued against the manufacturer after several inspections citing continued compliance violations and continued failures to comply with regulations. The agreement usually follows many FDA inspections where significant violations of GMP regulations related to facilities, manufacturing, quality assurance, equipment, laboratories, and packaging and labeling. The manufacturer may acknowledge the issues of non-compliance and agree to take corrective action for these areas that are stated in the Complaint for Injunction.
The Consent Decree, filed in the regional court where the company is located, will usually result in a monetary fine paid by the manufacturer for profits earned while the company was cited for noncompliance and continued to operate under such noncompliant conditions. The agreement may state that the company agrees to measures to assure that products manufactured are in compliance with regulations; companies have agreed to submit comprehensive work plans for each facility for FDA concurrence, station trained personnel at each facility who will provide full-time oversight of all operations at the facilities, and have their expert consultants conduct yearly inspections of the facilities for several years.
The manufacturer may be required to conduct regular audits of its operations and make reports to FDA concerning its continuing compliance, and FDA will periodically inspect manufacturing operations to evaluate the regulatory status of those operations. Manufacturers will generally be required to strengthen quality assurance and control programs, assess management controls and organizational structure to assure compliance with FDA requirements, to improve the internal audit system, and to improve the system of production and process controls. An agreement to suspend manufacturing [Cease and Desist of Operations] in other product lines many accompany this decree, as the company would have demonstrated a history of failing to comply with regulations and has documented extensive violations. "Manufacturers who choose to wait until FDA investigators find violations rather than policing themselves will find that they have made a poor and costly decision," said Dr. Lester M. Crawford, FDA's Deputy Commissioner.
The Consent Decree, filed in the regional court where the company is located, will usually result in a monetary fine paid by the manufacturer for profits earned while the company was cited for noncompliance and continued to operate under such noncompliant conditions. The agreement may state that the company agrees to measures to assure that products manufactured are in compliance with regulations; companies have agreed to submit comprehensive work plans for each facility for FDA concurrence, station trained personnel at each facility who will provide full-time oversight of all operations at the facilities, and have their expert consultants conduct yearly inspections of the facilities for several years.
The manufacturer may be required to conduct regular audits of its operations and make reports to FDA concerning its continuing compliance, and FDA will periodically inspect manufacturing operations to evaluate the regulatory status of those operations. Manufacturers will generally be required to strengthen quality assurance and control programs, assess management controls and organizational structure to assure compliance with FDA requirements, to improve the internal audit system, and to improve the system of production and process controls. An agreement to suspend manufacturing [Cease and Desist of Operations] in other product lines many accompany this decree, as the company would have demonstrated a history of failing to comply with regulations and has documented extensive violations. "Manufacturers who choose to wait until FDA investigators find violations rather than policing themselves will find that they have made a poor and costly decision," said Dr. Lester M. Crawford, FDA's Deputy Commissioner.
