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U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

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Leiner Health Products Response Letter


901 E. 23rd Street
Carson, California
Fax 310/835-6615

September 20, 2007


Serene N. Ackall
Compliance Officer
Atlanta District
U.S. Food and Drug Administration
60 - 8th Street, N.E.
Atlanta, Georgia 30309


Dear Ms. Ackall:

On August 28, 2007, Leiner Health Products LLC (Leiner or the Company) received a Warning Letter (07-ATL-10) as a result of the Fort Mill Inspection conducted from January 22 to March 16, 2007. We at Leiner want to reiterate that we take the Form 483 observations and the issuance of this Warning Letter with the utmost seriousness and want to assure the Agency that we are deeply committed to resolving our compliance issues, to bringing about a "cultural change" at Leiner and to putting systems, processes and knowledgeable and experienced individuals in place to sustain full cGMP compliance at all of our OTC facilities.

Request to Correct the Record

Leiner appreciates the District's acknowledgement of the corrective actions already taken and planned, as we have worked very hard to establish and deliver on our commitment to work closely and cooperatively with the Agency. Since the inspection, Leiner has tirelessly worked to conduct itself according to three overarching principles and company imperatives:

1. Protect the consumer.
2. Cooperate with and seek concurrence with FDA to ensure quality products from Leiner in the marketplace; return Leiner to good standing the FDA.
3. Achieve self-correction through the process of corporate culture change and remediation.

We wish to acknowledge our continued dialogue with the District and the frank and open communications we have had together since March 16. We especially appreciate the District's commitment to continue to work with Leiner as we proceed to re-enter the OTC marketplace. We reaffirm our commitment not to resume OTC operations without FDA's concurrence.

At the same time that Leiner has pursued a course of open, candid and constructive dialogue with the FDA, we have similarly kept our other key partners (i.e., customers, suppliers, employees, and investors) informed of the seriousness of the inspection findings and the major actions Leiner is taking to address its issues and to resume its good standing with them and the FDA. We have informed our business partners of the precautionary nature of our voluntary OTC drug product recall, our voluntary shutdown of the [redacted] OTC production facilities, and our ongoing commitment to restart OTC operations only with the concurrence of the FDA. We are thankful that our business partners have been very supportive of our explanations and consistent commitment to address our problems in a manner that enables our return to a position of leadership in the supply of high quality OTC products to its customers in good standing with the FDA.

We are concerned about some of the statements in the Warning Letter which, individually and collectively, could be misinterpreted as inconsistent with Leiner's expressed commitments and behavior following the inspection. We understand the potential for confusion and misunderstanding in view of the dynamic environment surrounding an adverse inspection and the voluminous exchange of information between Leiner, the District and other FDA offices. In our view, this likely has contributed to the following three statements in the Warning Letter that may reflect potential misunderstandings of Leiner's actual commitments behavior, and actions:

1. The Warning Letter states on page 1, that "Your own review of test data revealed a`highly unusual trend' for discrepancies and `numerous previously undetected failures', findings that prompted your decision to voluntarily recall your drug products."

Leiner Response: The Company's decision to voluntarily recall its drug products had absolutely nothing to do with Leiner's reviews or findings. Leiner's decision to initiate the voluntary recall was made on March 27, 2007, one day after our first meeting with the Atlanta District on March 26, 2007. I personally ordered this action as a precautionary measure to protect consumers in alignment with the FDA Atlanta District, and not as a result of internal reviews. As stated in our follow-up letter dated March 29, 2009 (Attachment I), this action was taken out of an abundance of caution after realizing the time it would take to complete the review of the potential impact of the inspection findings on the quality of the distributed lots. Leiner immediately took this voluntary action out of an abundance of caution and to demonstrate its good-faith to the FDA, the consumers and its customers.

2. The Warning Letter states on page 2 that "You are continuing packaging operations at your Fort Mill site. Under the law, packaging is also defined as a`manufacturing' operation". Further, on page 5 the Warning Letter states, "you expressed your intention to continue primary packaging (blisters) at the Fort Mill site of those bulk products currently stored at the site."

Leiner Response: No OTC packaging (i.e., bottles, blisters, etc.) has occurred in any Leiner facility since the week of March 26, 2007. All product shipments ceased on March 20, 2007. It was clearly stated in our Form 483 response letter dated April 9, 2007 that, on March 20, 2007, Leiner committed to the " . . .orderly suspension of all production and distribution of drug products." (Attachment II). Therefore, on March 20, 2007 Leiner ceased all distribution of OTC products from [redacted]. In-process packaging of WIP (work in process) was taken to final completion during the week of March 26"'.at both Fort Mill, SC and [redacted] facilities.

3. The Warning Letter states on page 5, "We understand that you intend to move the manufacturing operations previously conducted at the Fort Mill site to the [redacted] site by the end of September 2007 . . . . In addition because part of your corrective action plan is to simply move your manufacturing operations from Fort Mill, where the non compliance occurred, to your other sites, we request that you explain your plans for ensuring compliance with all laws . . . ."

Leiner Response: We are disappointed that the Warning Letter does not acknowledge the repeated and numerous commitments Leiner has made to the District, verbally and in writing, not to resume operations in any of our locations without close advance coordination with the FDA. As presented in our correspondence and meetings with the District, it was never Leiner's intention to simply move Fort Mill's operations to another site. Leiner was forced for business reasons to close its Fort Mill facility to reduce costs due to the voluntary suspension of its OTC business after receipt of the FDA's Form 483 [redacted] were lost as a result of this incredibly difficult and complex decision.

Leiner's consistent commitment to the District has been to complete a comprehensive program of assessment and corrective actions at each production location prior to resuming OTC operations and to seek the District's concurrence before resuming distribution. This commitment was made at our meeting with the District on March 26th, in the written response to the Form 483 dated April 9 (Attachment II), and at the August 15"' meeting with the District where Leiner's new Senior Vice President of Quality & Compliance, John Johnson, presented an overview of our new Site Master Compliance and Site Compliance and Restart Plans (Attachments III-VII). As part of its restart plans, Leiner requested, and the District agreed, to inspect the [redacted] site when operations resume and prior to Leiner's distribution of new product. We are grateful that the District also indicated it would coordinate within the FDA to seek a similar inspection of the [redacted] site before resuming distribution of OTC products.

We are concerned that these three misunderstandings in the Warning Letter will convey an unfavorable impression of our post March 16 conduct that, in our view, is inaccurate and not reflective of the objective, collaborative and constructive conversations Leiner has had with the District. Clearly, our business partners and the general public will be confused if the FDA elects to make this Warning Letter public, as presently written. The potential damage to Leiner is significant unless the FDA and Leiner can somehow prevent or mitigate these potential misunderstandings by the public. This is a critical issue for Leiner. As I discussed with the District on September 14, 2007, Leiner wishes to work with the District to respectfully and accurately clarify the record on these three points.

Specific Responses to the Warning Letter

This response will focus on key current commitments and actions, and refer to the enclosed Attachments for details with respect to prior responses, commitments and actions taken. Key strategic actions, both complete and anticipated, are summarized below:

Strategic Actions

• Leiner made an immediate decision following receipt of the Form 483 on March 19 to suspend production and distribution of OTC products at [redacted] sites ([redacted] Fort Mill [redacted]) and a commitment not to resume these operations without concurrence from the FDA. On June 6, 2007 Leiner informed the District that Fort Mill production and testing operations were being closed. Leiner's return to OTC operations at its [redacted] sites is being governed by our new Quality Systems Enhancement Action Plan (QSEAP), our new Site Master Compliance Plans and our new Site Restart Plans (See Attachments III-VII). [redacted]- will verify the completion of each element of the Restart Plans. The District has agreed to inspect [redacted] the site prior to Leiner's distribution of new product, and Leiner will also request and advance FDA inspection of its [redacted] facility.

• Leiner made a commitment on March 27 (immediately after the first meeting with the District) to conduct a voluntary recall of all Leiner OTC products, while product test data could be thoroughly reviewed. Leiner has substantially completed all of the voluntary recall, and will notify the District to witness the destruction and seek concurrence prior to any destruction activities concerning the recalled product.

• Leiner retained [redacted], an experienced and respected independent third party consultant, to help Leiner implement corrective actions and independently review suspended inventory for destruction or re-launch. [redacted] continues to assist Leiner as it develops, implements, and verifies the adequate completion of its corrective action plans. [redacted] continues to perform the third party Product Quality Assessments (PQAs), to determine the suitability of suspended inventory for potential distribution . Leiner will continue to work closely and cooperatively with the District to assure the rigor of the PQA process and product decisions.

• Leiner elected to take a holistic approach to assess not only its compliance and quality status, but also to evaluate the Leiner culture at its Fort. Mill [redacted] sites. This was accomplished through the use of independent third parties. The actions being taken by Leiner at its sites are a result of both the compliance and cultural evaluations.

cGMP Root Cause Activities

With respect to the specifically enumerated observations in the Warning Letter, we recognize their seriousness and have previously responded to them in our response to the Form 483 dated April 9, 2007 (Attachment II). We understand that your repetition of these observations in the Warning Letter emphasizes your concerns about the inspection findings. Summarized below are key actions being taken by Leiner to address the root causes of these inspection findings and to provide ongoing assurance of operational integrity and sustainable compliance with cGMP and product quality requirements:

• Leiner has restructured its Corporate and Site Quality Units from the top down (Attachment VIII-QA Org. Chart). This restructuring is consistent with cGMP principles and current industry practice, and considers the results of the independent assessment of "culture" and management control that were previously reported to the District. In addition to the termination of certain mid and senior level personnel, new key positions have been created and filled, including:

-New Senior VP of Quality & Compliance, reporting directly to the CEO and responsible for assuring the compliance of the Leiner product line with cGMP and product quality requirements. John Johnson was hired to fill this position on July 26, 2007. (Attachment IX-John Johnson's Job Description and CV).

-New Corporate Quality VP positions, reporting directly to the Senior VP of Quality & Compliance, including a VP of Validation, VP of Compliance & Quality Systems, and VP of QA/QC. These positions are responsible for providing the direction, oversight and assurance of conformance to cGMP and product quality requirements within their areas of purview. We have hired our new VP of Compliance & Quality Systems (Michael Ferrante) and the new VP of Validation (Robert Del Ciello). We are extremely pleased with these new hires, each of whom has significant relevant OTC pharmaceutical experience, and we look forward to their immediate contributions. They started work on September 17, 2007. ( Attachment X provides their CVs).

-New quality leadership positions at each OTC site, including: a QA/QC Director, separate QA and QC Managers, and a Site Compliance Manager. The site QA and QC managers report to the site QA/QC Director, who reports directly to the new corporate VP of QA/QC. The site Compliance Managers report directly to the new VP of Compliance & Quality Systems.

-In addition, Leiner has and will continue to make personnel changes, where appropriate, to assure that personnel are qualified and adequately trained to perform assigned management, supervisory and operating responsibilities leading to restarting operations.

• Leiner is establishing new programs and communications pathways to assure that members of corporate and on site quality management are informed of significant indicators of compliance and product quality issues. This will include a formal monthly and for-cause reporting of key quality information by the sites. Key Quality Indicators (KQI) from each site will become part of monthly QA reports to the Senior VP of Quality & Compliance. These KQIs will include such items as: customer complaints, OOS trending, product deviation trending, field alerts, recalls, and lab excursions reporting. These reports will be compiled by the Senior VP of Quality & Compliance and submitted to Leiner's Executive Management including the CEO. A Corporate Policy/Guideline is being developed that describes these new procedures and requirements. In addition, steps are being taken to assure that site and corporate cGMP internal audit programs are robust and executed by qualified personnel, that findings are communicated to top management, and that effective and timely corrective and preventive actions are taken to address any issues found.

• Leiner is committed to third party oversight of Leiner plans and activities to address commitments, including the overall program for strengthening and assuring cGMP compliance, product quality and integrity of operations. We have engaged, and are working closely with, [redacted] as we establish and implement a program of corrective action in support of the future restart of OTC production and/or testing operations.

• Leiner has commenced, together with [redacted] an assessment of the status of Leiner's OTC drug facilities, equipment, systems, procedures, controls and documentation practices to ensure conformance to cGMPs prior to restart of OTC operations. These assessments and all required corrective actions are being performed under individual Compliance Plans, which were discussed at our August 15th meeting with the Agency and are summarized below.

-Quality Systems Enhancement Action Plan (QSEAP) (Attachment III)

This is the governing document for Site Master Compliance Plans. This document defines the responsibility of each member of Leiner's executive management, including the CEO, in the execution of the Site Master Compliance Plans and Site Restart Plans (described below). A Steering Committee chaired by our new Senior VP of Quality & Compliance will oversee the execution of QSEAP. This document has been approved by the CEO and the new Senior VP of Quality & Compliance.

-Site Master Compliance Plans [redacted] (Attachments IV and V)

These plans utilize the Quality System Approach in evaluation of our OTC activities at our [redacted] facilities. Each Site Master Compliance Plan has been approved by the site Head of Operations, Head of QA/QC, and the Senior VP of Quality & Compliance at Leiner, after input from Leiner's Executive Management.

-Site Restart Plans [redacted] (Attachments VI and VII)

The Site Restart Plans are specific to the restarting operations at the site. Each contains a specific checklist and verification steps for such key areas as Quality Management SOPS, lab validations (addressing both equipment and methods), utilities and product specific validation. The Restart Plan also includes verification of operator and QA training. Each plan has been approved by the site Head of Operations, Head of QA/QC, and the Senior VP of Quality & Compliance at Leiner, after input from Leiner's Executive Management.

No OTC restarts will be initiated unless and until [redacted] has verified the adequate completion of each element of each of these plans and we have completed all appropriate coordination with the District well in advance. Upon start-up, each product/process will undergo a concurrent revalidation, including placing the first three lots on concurrent stability (three lots room temperature, of which one will be accelerated).

• As noted above, Leiner has arranged to perform Product Quality Assessments (PQAs) to determine whether inventory voluntarily removed from the distribution chain at Fort Mill, [redacted] was manufactured, packaged and tested in conformance with cGMPs and product quality requirements, and to verify the assigned expiration dates. A number of these products are actually manufactured by third parties (bulk tablets).

[redacted] is performing the required third-party reviews and oversight functions under the PQA process. This includes a protocol-driven evaluation of historical product/process performance, review of selected batch records and test results, evaluation of stability data, and the performance of current testing of selected lots under adequate cGMP controls using suitable and adequately validated test methods. Leiner is hopeful that these comprehensive PQA reviews will enable the distribution of lots determined to adequately meet requirements. Lots found not to meet requirements will be destroyed. The approach has been the subject of discussions with the District, including most recently the meeting on August 15, 2007 and the follow-up Leiner correspondence. As discussed, Leiner commits to not distributing any suspended inventory unless the District concurs that the POA process is adequate. Leiner will continue to submit PQAs to the Agency on a product-by-product bases until such time that the Agency gives concurrence for Leiner to "self-administer" the PQAs under third nary oversight. Any lots found not to be acceptable for distribution will be destroyed. Leiner will notify the Agency to provide FDA with the opportunity to witness product destruction.

• Leiner has implemented new Training Programs to address the findings described above and support our OTC restart. We recognize the critical importance of a sound, effective training program as a key element of a sustainable compliance program.

-Ethics training was performed and conducted by third party trainer of the for all Scientific Affairs (QA/QC, Regulatory, Compliance, New Product Development) personnel the week of February 12, 2007 in the Fort Mill and [redacted] facilities. The same training was conducted the week of April 16, 2007 in [redacted]. Additional training will be completed at all sites by the end of December 2007 for all Leiner employees once ongoing revisions to the Standard of Conduct Policy are completed. The Policy will cover all issues pertaining to ethics. Annual retraining for all OTC and VMS supervisors and management will be implemented, and training will be required for all new hires.

-Investigation Training was conducted by [redacted] (Consultant) at both the Fort Mill facility (week of March 26, 2007 and April 16, 2007) and at the [redacted] facility (week of May 2, 2007) for QA and Operations personnel responsible for performing investigations for manufacturing and packaging. Additional investigation training will be performed at the [redacted] site by October 2007.

Laboratory training for new SOPs was initially conducted by in-house QA personnel the week of June 25th in Fort Mill and the week of June 19th in [redacted].

-A cGMP course will be performed at both [redacted] the facilities prior to restart for all Operations and Quality personnel. The cGMP training will cover all subparts of the cGMPs.

Response to Additional Concerns

To the extent that any restart plans involve the movement to another facility of production, packaging or testing operations required to be performed under an approved ANDA (versus bulk purchased for repackaging), Leiner will notify each affected sponsor in writing of Leiner's intention to site transfer the sponsor's product to another Leiner facility. Leiner will provide the Agency a copy of sponsor notifications as they occur. In addition, for any Leiner ANDA product, Leiner will file the appropriate ANDA supplement to the Agency regarding any transfers to another facility. This will be managed by Leiner's Corporate VP of Regulatory Affairs. To date no decision has been made as to any planned site transfers that will require this type of notification and/or filing.

Leiner Health Products continues to be fully committed at all levels within the organization to meeting and sustaining cGMP compliance at all Leiner OTC facilities. We sincerely appreciate the Agency's support as we move toward full, sustainable compliance and the ultimate return to the OTC market. We would welcome an opportunity to further meet with the District, or any other FDA office, to clarify the record and insure our commitment to return Leiner to good standing with the FDA.

If you have any questions or require additional information please feel free to contact me at (310) 952-1339 or John Johnson, our Senior VP of Quality & Compliance at 252-296-4139 or by mobile at [redacted]



Robert M. Kaminski
Chief Executive Officer
Leiner Health Products