by Barbara Unger, FDAzilla GMP Quality Expert

INDIA | IMPORT ALERT 66-40 and Association with Warning Letters Regarding These Sites | Detention Without Physical Examination of Drugs from Firms Which Have Not Met Drug GMPs

In this post, I consider the active import alerts in the “66-40” category currently posted on the FDA website for firms located in India and the frequency with which warning letters are associated with the import alerts. The tabulated data does not identify import alerts that may have been put in place and removed within this time period. Addresses are often difficult to unambiguously align, but I’ve made every attempt to do so. Where warning letters have been issued, most link(s) are provided.

FROM THE FDA WEBSITE DESCRIBING IMPORT ALERT 66-40: “Foreign inspections of pharmaceutical manufacturers are being performed. Detention without physical examination may be appropriate when an FDA inspection has revealed that a firm is not operating in conformity with current good manufacturing practices (GMP’s).

Detention without physical examination (DWPE) may also be appropriate when the FDA receives information concerning inspections conducted by foreign or other government authorities under a Memorandum of Understanding or other agreement that reveals conditions or practices warranting detention of either particular products or of all products manufactured by a firm.

DWPE of such firms remains in effect until such time as the FDA is satisfied that the appearance of a violation has been removed, either by re-inspection or submission of appropriate documentation to the responsible FDA Center.

CONCLUSION:

• Currently 41 sites in India are under import alert for failure to comply with GMPs (Table 3).
• For these 41 sites, twenty-one of them, just under half do NOT have associated warning letters. Thus, being placed under import alert is no guarantee that a warning letter will be issued regarding the site nor is receiving a warning letter a guarantee of an import alert (Table 1).
• Among the active import alerts in this category, four have been issued to a single company, one firm has 3 sites under import alert, nine (9) firms have two sites under import alert and sixteen (16) have a single site under import alert. The firm with four sites is Sun Pharmaceuticals, and this includes sites that Sun acquired in their purchase of Ranbaxy Pharmaceuticals (Table 2).
• In three instances, EU reports of GMP non-compliance issued based on inspections in a similar timeframe. They are identified in Table 3 and summary reports may be found HERE.

TABLE 1: Import Alerts per Calendar Year

YearNUMBER of AlertsImport Alerts With Associated Warning LettersImport Alerts Without Associated Warning Letters2009220201000020116242012000201314592014871201511472016000TOTAL to 3/26/2016412021

Figure 1. Import Alerts by Year and Those Without Associated Warning Letters

TABLE 2: Active Import Alerts (66-40) per Company Site in India, 2009 – 2016 to date

COMPANYNUMBER of SITESSun Pharmaceuticals (includes sites that were previously Ranbaxy sites)4Ipca Laboratories3Wockhardt, RPG Life Sciences, Nivedita Chemicals, Flemming Laboratories, Vignesh Life Sciences, Apotex, Pan Drugs, Micro Labs, Aarti Drugs Limited2 sites for each firm

(9 companies, 18 total alerts)

Stericon, Yag Mag Labs, Amsal Chem Pvt Ltd, Smruthi Organics, Sentiss Pharma, Unique Chemicals, Kamud Drugs, Konduskar, Aadivighnesh Chem, Canton Laboratories, Marck Biosciences, Emcure Pharmaceuticals, Sri Krishna Pharmaceuticals, Akorn India, Polydrug Laboratories, Magafine Pharma1 site for each firm(16 total)

Table 3: Listing of firms/sites in India currently under Import alert 66-40, by Date of Issue

Links are provided to associated warning letters on the FDA website

COMPANYSITEDATEOTHERSun Pharmaceutical (previously Ranbaxy)Village Ganguwala, Tehsil, Paonta Sahib, Simour District, Himachal Pradesh INDIA9/10/2009ArchivedSun Pharmaceutical (previously Ranbaxy)Industrial Area No. 3, Madhya Pradesh, Dewas, Madhya Pradesh INDIA9/10/2009ArchivedStericon Pharma Pvt. Ltd.No. 9, Sub Layout Of Plot 9, 1st Phase Bommasandra Ind. Area, Bangalore, Karnataka, INDIA1/13/2011ArchivedFleming Laboratories Ltd.Survey 270, Navabpet Village, Medak, Andhra Pradesh INDIA4/8/2011No warning letter posted. This site was the subject of a EU GMP report of non-compliance by the French authorities based on an inspection of October 11, 2013.Fleming Laboratories LimitedPlot No. 48, Temple Rock Enclave, Tarbund X Road, Secunderabad, INDIA4/11/2011No warning letter postedYag Mag Labs Private LimitedSurvey No. 10, Gaddapotharam Village, Jinnatam Mandel, Medak District, AP, INDIA9/13/2011ArchivedNivedita Chemicals P lTdA14 MIDC Andheri East, Mumbai, IN-MH INDIA11/23/2011No warning letter postedNivedita Chemicals Pvt. Ltd.A-14 M.I.D.C. Andheri (East), Maharashtra, MS INDIA11/23/2011No warning letter postedAmsal Chem Pvt. Ltd.A-1/401-402-403, GIDC, Ankleshwar, Gujarat, INDIA4/11/2013No warning letter postedWockhardt LimitedPlot H-14/2, Biotech Park, M.I.D.C. Area Waluj, Aurangabad, Maharashtra INDIA5/22/2013Warning Letter, July 18, 2013Smruthi Organics LimitedPlot No. A-27, MIDC, Chincholi, Solapur District, Maharashtra, INDIA6/3/2013Warning Letter, March 6, 2014 This site was the subject of an EU GMP non-compliance report based on an inspection by authorities of the Netherlands, conducted on Oct 16, 2013.RPG Life Sciences Limited25, M.I.D.C. Land, Thane-Belapur Road, Thane, Maharashtra INDIA6/10/2013Warning Letter, May 28, 2013RPG Life Sciences Limited3102/A G.I.D.C. Estate, 393002, Ankleshwar, Gujarat INDIA6/11/2013Warning Letter, May 28, 2013Sentiss Pharma Pvt. Ltd.Village Khera Nihla, Tehsil Nalargarh, District Solan, Himachal Pradesh INDIA6/20/2013No warning letter postedUnique ChemicalsPlot P-10, Shiv Mahape Gansoli, Thane Belapur Road, Maharashtra State, Rabale, Maharashtra INDIA6/28/2013No warning letter postedVignesh Life Science Pvt Ltd202 Sarada Residency, H – 26, Madhura Nagar Ameerpet, Hyderabad, Tamil Nadu INDIA6/28/2013No warning letter postedVignesh Life Sciences Pvt., Ltd.93 & 94 P Mundargi Industrial Estate, Bellary Karnataka, INDIA6/28/2013No warning letter postedKamud Drugs Pvt. Ltd.N-608, MIDC, Kupwad, Sangli, M.S., INDIA7/10/2013No warning letter postedKonduskar Laboratories Pvt LtdT-47 Kagel Hatkanangale Five Star, MIDC, Talandage (Village), Tal: Kagal, Maharashtra State, INDIA7/10/2013No warning letter postedMicro Labs LimitedPlot No. 113-116 4th Phase KIADB, Bommasandra Industrial Area, Anekal Taluk, Bangalore, INDIA8/21/2013No warning Letter postedSun Pharmaceutical Industries (prev. Ranbaxy)SEZ Unit 1, Plot No. A-41, Industrial Area Phase VIII-A, SAS Nagar, Mohali, Punjab INDIA. This site and data are listed twice on the FDA site but are listed here only once.9/13/2013No warning letter postedWockhardt LimitedL-1, MIDC Area, Jalgaon Road 43, Chikalthana, Aurangabad, Maharashtra INDIA11/26/213Warning Letter, November 25, 2013Marck Biosciences Ltd.Plot No. 876, N.H. – 8, Vill: Hariyala, Tal: Matar, Kheda, Gujarat INDIA3/12/2014ArchivedSun Pharmaceutical Industries Limited – KarkhadiPlot No. 817/A, Village – Karkhadi, Taluka – Padra District, Vadodara, Gujarat, INDIA3/12/2014Warning Letter, May 7, 2014Ipca Laboratories Ltd1 Pharma Zone, Pithampur, Madhya Pradesh INDIA3/25/2014Warning Letter, Jan 29, 2016Apotex Pharmachem India Pvt Ltd.Plot No.: 1A, Bommasandra, Industrial Area, 4th Phase, Bangalore, INDIA4/1/2014Warning Letter, June 16, 2014Canton Laboratories Pvt. Ltd.110 A & B Gidc Estate, Makarpura Road; M I Estate, Vadodara, Gujarat INDIA4/10/2014Warning Letter, February 27, 2014Aadivighnesh Chem PVT. LTD.A/7 Badrinath Apartment, Simpoli Road, Borivali (West), Mumbai, Maharashtra INDIA5/5/2014No warning letter postedMicro Labs LimitedS – 155 Plot No, Verna Industrial Estate, Vasco Da Gama, Goa INDIA9/19/2014Warning Letter, January 9, 2015Apotex Research Private LimitedPlot 1/2, Site #2 Bommasandra Ind. Area, 4th Phase, Jigani Link Rd., Jigani Hobli, Bangalore, Karnataka State INDIA9/22/2014Warning Letter, January 30, 2015Ipca Laboratories LimitedVillage Sejavta, Ratlam, Madhya Pradesh INDIA1/22/2015Warning Letter, Jan 29, 2016Aarti Drugs LimitedPlot No. E-22, M.I.D.C., Tarapur, Palghar, Maharashtra INDIA3/23/2015Only Warning Letter is a previous one dated July 30, 2013Aarti Drugs LimitedG-60 Boisar MIDC Tarapur, Tal. Palghar, District Thane, Tarapur, Maharashtra INDIA3/23/2015Only Warning Letter is a previous one dated July 30, 2013Ipca Laboratories Ltd1 Pharma Zone, Pithampur, Madhya Pradesh INDIA3/24/2015Warning Letter, Jan 29, 2016Ipca Laboratories LtdPlot No. 65 and 99, Danudyog, Ind. Estate, Piparia, Silvasa (D and NH), INDIA3/24/2015Warning Letter, Jan 29, 2016Pan Drugs Ltd.167-168, GIDC Nandesari Ind. Estate, Nandesari, Vadodara, Gujarat INDIA5/5/2015Warning Letter, September 2, 2015Emcure Pharmaceuticals LimitedPlot No. P-1 & P-2, IT-BT Park Phase II, MIDC, Hinjwadi, Hinjwadi, Pune, Maharashtra INDIA7/13/2015Warning Letter, March 3, 2016,Sri Krishna Pharmaceuticals Ltd. – Unit IIA-35, IDA, Nacharam, Hyderabad, Andhra Pradesh, INDIA8/13/2015No warning letter posted. An EU Summary Report of Non-compliance was issued based on an inspection of December 4, 2014 conducted by Italian authorities.Akorn India PVTKhasra 5/1, 5/2, 5/3 Village, Nihalgarth Tehsil, Paonta Sahib, Simour, Himachal Pradesh INDIA8/21/2015No warning letter postedPolydrug Laboratories Pvt. Ltd.Plot N37, Ambernath Industrial Area, Anand Nagar MIDC, Mumbai, Maharashtra INDIA9/11/2015No warning letter postedMegafine Pharma (P) Limited48 – 51/201 Plot No 31 – 35, Lakhamapur, Maharashtra INDIA10/14/2015No warning letter postedPan Drugs Limited192 G I D C Makarpura Industrial Estate, M I Estate, Vadodara, Gujarat INDIA12/08/2015No warning letter posted