Lane, conducted. NJ, February 23 through March 22, During the investigator. inspection documented

Transcription

1 DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Food Drug Administration Central Region G Telephone (973) New Jersey District Waterview Corporate Center 10 Waterview Blvd, 3` Floor Parsippany, NJ July 11, 2006 WARNING LETTER CERTIFIED MAIL RETURN RECEIPT REQUESTED Mr N K Rao Ramanadham, R Ph President Concord Laboratories, Inc 140 New Dutch Lane Dear Mr Ramanadham : An inspection your manufacturing facility located at 140 New Dutch was Lane, conducted Fairfield, from NJ, February 23 through March 22, 2006 During investigator inspection documented our deviations from Current Good Manufacturing Regulations, Title Practice 21 Code (CGMP) Federal Regulations, Parts ) 211 (21 CFR 210 manufactured tested at this site These deviations to cause be adulterated your within meaning Section 501(a)(2)(B) Food, Drug Federal Cosmetic Act ( Act) (21 U SC 351 (a)(2)(13)) 1) Written records are always made investigations into unexplained discrepancies, nor did investigations unexplained discrepancies extend to or batches same product or or that may have been associated with specific failure or discrepancy [21 CFR ] Specifically : a) Product samples tested in conjunction with a complaint regarding on loose Nitroglycerin caps tablets, lot , produced out--specification assay results content unimity There was no examination or a review product retains batch record The sample results were product invalidated damage due to from environmental exposure although re was provision no this in your firm's written procedures b) Product samples tested in conjunction with complaints regarding dissolving tablets Nitroglycerin tablets, lots , all release were tested specifications except assay There was no omission justification this test, nor was re any evidence an stability examination lots, retained samples, or a review batch c) The records reference stard injection following assay content testing unimity Hyoscyamine Sulfate Tablets, lot P3274, failed due to show to a leaking any column peaks There was no documented investigation deviation, re was this no assessment impact leaking column Hyoscyamine on Sulfate analysis or any or analysis conducted same column, with Hyoscyamine samples were reinjected This same

2 Page 2 observation was made during previous inspection, yet was no conducted investigation d) There was no documented investigati n regarding HPLC requiring malfunctions external repair Both HPLCancarequired repair however in June re is no 2005 ; documentation regarding wher impacted malfunctions any analyses, if so, what corrective actions those were analyses regarding e) The investigation into an out-=specification assay result Diphenhydramine Tablets concluded cause to be a dilution error result as a use incorrect glassware This conclusion could be supported as actual glassware used was documented procedures laboratory do require that glassware be maintained until analysis complete is f) Power failures occurred during analyses Nitroglycerin, lot Senna , S, lot Investigations did document impact analyses, on any re-testing or resampling, or if power outage or impacted analyses any 2) Laboratory records fail to include initials or signature person each laboratory who test [21 perms CFR (a)(7)] S ecifically, laboratory records analysis analyses permed on HPLCs*nd~do indicate permed which analyst irnjections 3) Failure to maintain complete records any modification an established method employed in testing [21 CFR (b)] Specifically, records laboratory methods stored in Mll 1-11 ;omputer system do include identity person initiating method changes 4) Appropriate controls are exercised over computers or related systems to assure that changes in analytical methods or or control records are instituted only by authorized personnel [21 CFR (b)] Specifically : a) Laboratory managers (QC R&D) gained access to computer system through a common password MOM Analysts were to use individual required passwords; y operated system following laboratory login by managers b) Due to common password lack varying security or levels, any manager has analyst access to, can modify any HPLC analytical record method or Furrmore, review audit trails is required 5) Failure to follow written procedures applicable to quality control, unit [21 CFR (d)] Specifically, contracted laboratories responsible perming analyses on Active Pharmaceutical Ingredients or components, used in finished, such as LOD, nitrogen content; microbial limits, specific rotation, have been qualified by quality unit as per your firm's written procedures 6) Failure to maintain separate or defined areas or or such control systems as are necessary to prevent contamination mix-ups in course manufacturing processing operations [21 CFR (c)(5)] Specifically, no monitoring

3 Page 3 system is conducted to demonstrate that volume air supplied is sufficient to maintain appropriate air pressure differentials between manufacturing rooms, corridors, pharmacy rooms 7) Failure to provide adequate measures to control air contamination recirculation dust from production areas where air is recirculated [21 CFR (c)] Specifically : a) No studies have been conducted to assure that system removes contaminants from production area that cross-contamination does occur b) Modifications made to air hling systems production rooms 6 8, to add exhaust ventilation, were qualified to show ir effectiveness at time installation 8) Failure to establish master production control records each product including a statement maximum minimum percentages oretical yield beyond which investigation is required [21 CFR (b)(7)] Specifically, actual oretical yields are calculated after tablet compression but your firm has established appropriate specifications acceptable yields 9) Test devices are deficient in that apparatus are meeting used [21 established CFR 211 specifications 160(b)(4)] Qualification studies temperature stability chamber "Wroom were deficient in that y did specifications, acceptance always include criteria, or raw data Specifically : a) There was no data to demonstrate that chamber as required alarm in would event perm a humidity excursion b) There were no specifications or acceptance or criteria water quality water to pressure chamber There are specific se requirements outlined in operating manual chamber ' 10) Failure tomaintain equipment at appropriate intervals to prevent malfunctions or contamination that would alter safety, identity, strength, quality or purity product [21 CFR (a)] Specifically, Packaging Hopper was found to be cracked Cracked equipmen can be easily cleaned to prevent cross-contamination between In addition, inspection revealed that certain in violation sections manufactured by 505(a) your firm 502(f)(1) are [21 U SC following 355(a) reasons : 352(f)(1)] Act, You manufacture following prescription : " Colchicine Tablets " Hyoscyamine Sulfate Tablets " Nitroglycerin Sublingual Tablets These are s within meaning 321(g)] section because 201(g) y are Act [21 intended USC use in prevention diagnosis, cure, disease mitigation, FDA is unaware treatment, or substantial as scientific manufactured evidence by that any your firm se are generally recognized by qualified experts as safe

4 Page 4 effective ir labeled indications Theree, y are "new s" within meaning section 201(p) Act [21 US C 321(p)] Section 505(a) Act [21 USC 355(a)] requires that any new be subject an FDA-approved new application bee it is introduced into interstate commerce There are no approved applications on file above ir continued marketing violates section 505(a) [21 U SC 355(a)] In addition, se s are misbred As prescription s, adequate be directions written m can so that a layman can use se safely ir intended Consequently, uses ir labeling fails to bear adequate directions use as required section under 502(f)(1) Act [21 US C 352(f)(1)], lacking required approved applications, y are exempt from this requirement under 21 CFR We have received your written response to FDA-483, dated May 3, 2006 This will be added response to our ficial files For reasons below, we do find this response sufficient Please to be e that comments below pertain only to CGMP exclusion observations ; a discussion responses to observations made about subject to ANDAs does mean that responses were assessment adequate An responses to ANDA-related observations will be cover sent under separate The response does include documentation to show that corrective actions implemented have (see FDA-483 been items 3, 4, 6, 8, 9, 11, 12) For example revised you did calibration submit procedures referenced in your response to addition, FDA-483 item some # 4 responses In to FDA-483 items (1 6) do include completion timeframes corrective action For example, your response to item new #1 password states that system will a be implemented but does specify a completion some date responses Also, fail to address underlying issues deficiencies inherent For in example, ed response to item # 2 states that results in-specification obtained test tested bee after various instruments failures show that analytical reliability analyses was impacted However, by obtaining failures in-specification test results from a product analysis indicate does suitability, by itself, analytical system used or reliability results The above identification violations is intended to be an all-inclusive at your list facility It deficiencies does include observations deficiencies which related to have ANDA yet been approved marketed It is your responsibility to ensure your that firm manufactures are in compliance with Act promulgated regulations under it Federal agencies are advised issuance about all warning letters so that y may take this inmation into account award when contracts considering Until FDA can confirm correction deficiencies most recent observed inspection, during this fice can recommend disapproval listing any this site new as a applications manufacturer s You should take prompt action to correct deficiencies at your facility result Failure in furr to do regulatory so may action without ice These actions may include or seizure injunction your You should ify this fice within 15 working days receipt this letter corrective actions you additional plan to implement to address deficiencies at your firm If

5 Page 5 corrective actions can be completed within 15 working days, please state reason delay time frame within which corrective actions will be completed Your response should be addressed to : U S Food & Drug Administration, 10 Boulevard, 3rd Waterview Floor, Parsippany, New Jersey 07054, Attn : Sarah A Della Officer Fave, Compliance Sincerely, Douglas I Ellsworth District Director New Jersey District