NATIONAL DRUG SURVEY. Chapter 9 Main Survey

Transcription

1 NATIONAL DRUG SURVEY Chapter 9 Main Survey

2 Main Survey 116 Ministry of Health & Family Welfare National Drug Survey

3 National Institute of Biologicals MAIN SURVEY The methodology of the main survey covered sampling procedure, sample collection, packaging, visual inspection, transport of samples to laboratories, reporting of results by the laboratories and digitization of data using AKS Software. Methodology was further improved based upon the outcome of pilot study, so that it now had a well defined purpose and scope, error free digital tools and clear understanding by stakeholders. PRE-DRUG SAMPLING PREPARATION Identification and training of sample drawing team Before beginning of the Drug sampling, Drug inspectors as Sample Drawing Officers (SDOs) and the representatives of Civil Society /Pharmacy Council of India who were to work as team were identified and trained. They were trained together so as to make them know each other and to understand as well as respect each others roles. They were to travel together for collection of samples. Trained SDOs were in-charge of the whole sampling effort. A specially developed animated video film was used to explain the methodology. Availability of physical resources Prior to visit, SDOs from each team were provided with two kits (Exhibit 9.1) through their respective Nodal Coordinating Officers i.e State Drug Controllers. Each SDO was provided with a list of Sources from where the samples were to be drawn. One Data Form per Source was also provided to SDO with the instruction to use only one Data Form for each Source. Each data form had a unique number which was specific to the SDO. Different colour schemes for data forms were used for Govt. Sources (pink) and Retail Outlets (white). Each SDO was also provided with a NIB Drug Survey brass seal which was engraved with a unique number for the respective SDO. This seal helped in tagging a particular sample to the SDO who had drawn it from a Source. SAMPLING PROCEDURE FOR RETAIL OUTLETS/GOVT. SOURCES Sampling procedure was divided into three broad steps (Exhibit 9.2) i.e. (1) Locating the Source, (2) Drawing of samples from the Source and feeding the data of the Source & sample particulars in the Data Form, (3) Packing the Ministry of Health & Family Welfare National Drug Survey

4 Main Survey Exhibit 9.1 Pre-sampling Preparation KIT 1 Adhesive Magnifying Glass Thread Envelope Candle Bubble wraps Sealing wax Scissors Carbon paper Rubber band Marker pen Stapler with pins Matchbox Large Envelopes Adhesive Tape KIT 2 Sampling plan and data forms Brass Seal with unique ID Circular 118 Ministry of Health & Family Welfare National Drug Survey

5 National Institute of Biologicals samples and posting them along with the Data Form to NIB after feeding the particulars in the AKS software. Training program was designed to ensure full adherence to the below given three steps:- Exhibit 9.2 Steps of Sampling Procedure 1 Locating the Source 2 3 Drawing of samples from the Source and feeding the data of the Source & sample particulars in the Data Form. Packing the samples and posting them along with the Data Form to NIB after feeding the particulars in the AKS software. (1) Locating the Source Each sample drawing team selected the Source from the list of assigned Sources according to the plan. After selection of the Source, team members mutually scheduled a visit to the Source as per address provided to them. Immediately after locating and reaching the source, activities of drawing samples were started as per the Sampling Procedure. In case, the Source did not exist at the mentioned location or was closed, then sampling team chose a Source that was nearest within a radius of 5 kilometres from the location of original Source. In case there were more than one Sources at the new location, the option of selecting one of these Sources was left to the representative of Civil Society /Pharmacy Council of India who was a member of the sample drawing team (Exhibit 9.3). As soon as the Source was confirmed, sample drawing team was to enter the shop and politely introduce themselves to the concerned person Ministry of Health & Family Welfare National Drug Survey

6 Main Survey EXHIBIT 9.3 STEPS FOR LOCATING THE SOURCE SELECT ONE OF THE ASSIGNED SOURCES AND GO TO THE LOCATION WITH YOUR TEAM IS THE SOURCE ACCESSIBLE? (NOT ACCESSIBLE IF IT DOESNOT EXIST OR CLOSED) NO YES LOCATE THE NEAREST SOURCE WITHIN 5 KM RADIUS YES COULD YOU FIND ANOTHER SOURCE THAT IS OPEN? NO UPLOAD THE REASON IN AKS SOFTWARE AND POST THE HARD COPY TO NIB TAKE THIS SOURCE FOR SAMPLE COLLECTION AND PROCEED FURTHER 120 Ministry of Health & Family Welfare National Drug Survey

7 National Institute of Biologicals at the source and present the circular provided by NIB describing the purpose of sampling for the survey. After introducing themselves the team was to draw Drug samples from the source as per the sampling procedure. (2) Drawing of samples from the Source, feeding the data of the Source & sample particulars in the Data Form. After locating the source and introducing themselves, the sample drawing team was to select the Drug formulations for sampling using data form. The data form consisted of five parts, i.e., A, B, C, D and E (exhibit 9.4). Exhibit 9.4 Contents of Data Forms Details of6selected Drug Molecules and signatures of team members and the concerned person from the Source. List of available formulations of each selected Drug Molecule PART A PART B PART C PART D PART E Details ofsource from where samples were drawn List of Drug Molecules for drawing of Samples Adequate Quantity of different dosage forms to be sampled The selection of formulation for sampling was to be made in a stepwise manner by filling up different parts of this data form as follows: Step 1. Selection of Drug Molecules for drawing of samples Step 2. Listing of all available formulations of the selected Molecules Step 3. Selection of one formulation for drawing as sample Ministry of Health & Family Welfare National Drug Survey

8 Main Survey STEP 1. Selection of Drug Molecules (DMs) for drawing of samples In the first step six DMs were to be selected for drawing of samples from a particular outlet. This selection was to be made from the list of 224 molecules which was placed as Part-C of the data form. These 224 molecules had distinct DM IDs and were placed in a randomised order from serial no. 1 to 224. Starting from serial number 1 of this list, SDOs were to mark each serial number with either a tick mark or a circle or a cross mark based on the following rules: Tick mark: for the serial number of the DM available at the Source against which there is at least one formulation having adequate quantity for sampling. Circle mark: for the serial number of the DM available at the Source against which there is at least one formulation having minimum primary packaging but no formulation with adequate quantity for sampling. Cross mark: on the serial number of the DM against which there is no available formulation at the Source. The SDOs were to stop marking the serial numbers of DMs as soon as six serial numbers were marked with a tick mark (Exhibit 9.5) or they exhausted the list up to 224 DMs. This would lead to following two situations: Situation1: Six DMs with tick marks (ü). This meant that six DMs with at least one formulation having adequate quantity for sampling were available at the Source Situation 2: Less Than Six tick marks. This meant that some DMs having adequate quantity (ü) and some having inadequate quantity (O)/ no formulation (X) for sampling available at the Source. 122 Ministry of Health & Family Welfare National Drug Survey

9 National Institute of Biologicals Exhibit 9.5 Showing a sample list of DMs having six tick marked drug molecules available in adequate quantity for sampling at an outlet Molecules available in drawing samples O Molecules available iin required for drawing samples X Molecules not available STEP 2. Listing of all available formulations of the selected molecules In second step listing of formulations of DMs selected using step 1 above was to be done using Part-D of the data form. Part-D contained a table with six columns marked as S1, S2, S6. The listing of formulations of the selected DMs was to be done in the following manner: Ministry of Health & Family Welfare National Drug Survey

10 Main Survey Listing the DM ID of six molecules: DM ID of the molecule which was tick marked first in serial order (using step 1) was to be written against Sample ID ending with S1. DM ID of the molecule which was second in the tick marked serial order was to be written against Sample ID ending with S2 and the procedure was repeated in the similar fashion till S6. In case of situation 2 mentioned above where less than six formulations with adequate quantity were available, the listing was to be started with DM with maximum quantity available at Source and continued with next highest quantity and so on (Exhibit 9.6). Listing the formulations against each DM ID: Under each DM ID, all available formulations of respective DM were to be listed. While listing the details of formulations, the brand name and strength was to be written for branded formulation whereas manufacturer s name and strength was to be mentioned for generic formulations. STEP 3. Selection of one formulation for drawing as sample After listing the formulations under each DM (using step 2), one formulation was to be selected using a random number which was printed at the bottom of the list of formulations of each DM. For the selection of formulation, firstly the number of formulations under each DM were to be counted. Suppose this number was q. Then the random number printed at the bottom of the column of each DM was to be divided with this number q. If r was the remainder so obtained, then counting from top, (r+1)st formulation listed in the column under that particular DM was to be sampled. A circle around the formulation selected for drawing as sample was to be made (Exhibit 9.6) and the total quantity available in the Source for this formulation was to be ascertained. If the total quantity available was more than adequate quantity, only the adequate quantity was drawn. In case adequate quantity was not available, then available unit packs were drawn. 124 Ministry of Health & Family Welfare National Drug Survey

11 National Institute of Biologicals Exhibit 9.6 Showing Part-D of data form listing formulations for drawing of sample 1. IDs of selected molecules available at the Source the one selected for sampling 3. Random number to be divided by number of column: Random no. (r) = 197 Remainder (q) obtained upon dividing (r/n) = 2 selected = (q+1)st = 3rd in the list, which is FLAMORYL. Ministry of Health & Family Welfare National Drug Survey

12 Main Survey Filling up particulars of sampled formulation Details of formulations selected for sampling were to be filled in Part-B of the data form. Contents of Part B included (Exhibit 9.7): Serial number of the selected DM as mentioned in Part-C (randomised list of 224 molecules) Labelled information including manufacturing, batch and licensing details. Signatures of team members and the authorized person from the Source 126 Ministry of Health & Family Welfare National Drug Survey

13 National Institute of Biologicals Exhibit 9.7 Showing Part B of data form containing details of formulation sampled from a particular source Ministry of Health & Family Welfare National Drug Survey

14 Main Survey Filling up of details of Source All the details related to Source from where samples were drawn along with the payment details towards the cost of the sample were to be filled in Part-A of data form (Exhibit 9.8). Thereafter, signatures of team members (representative of Civil Society /Pharmacy Council of India) and the authorized person from the Source were to be obtained. If the Source visited was not the same as the one assigned, then relevant entries were to be filled appropriately with remarks in the remarks box. However, the remark was to be co-signed by representative of Civil Society /Pharmacy Council of India at the designated place and the same remark was to be reflected while feeding the particulars in the Drug Survey- AKS software. While carrying out the sampling procedures, the representative of Civil Society /Pharmacy Council of India ensured that the atmosphere in and around the Retail outlet was congenial. 128 Ministry of Health & Family Welfare National Drug Survey

15 National Institute of Biologicals Exhibit 9.8 Showing part A of data form containing details related to Source from where samples were drawn Ministry of Health & Family Welfare National Drug Survey

16 Main Survey Sampling from Ports In case of Ports, sampling was done from each and every consignment imported through the notified ports in respect of finished Drugs formulations and Active Pharmaceutical Ingredient (API) pertaining to the list of 224 molecules identified for the Drugs Survey. Samples were drawn for a period of three months by CDSCO port offficers. Most of the consignments received were in the form of APIs and the type of packaging was either plastic containers or polyethylene bags of 25 kg or 50 kg. Further, Drugs in API form were of two types: sterile and non-sterile. For the non- sterile APIs, the samples were drawn at the ports at the time of receiving the consignments. The samples of sterile APIs were drawn under sterile condition by taking the containers to the manufacturer s site. For APIs, a sample was drawn from each API. For example, if there were 10 different APIs from the list of 224 molecules in one consignment, then 10 samples of APIs were drawn. If there were different batches within an API, then one sample from each API batch was drawn. Once the containers of an API of a particular form and particular batch were identified, the containers were numbered as 1, 2,, n, where n was the total number of containers. Three random numbers between 1 to n without replacement were selected using a mobile app provided for drawing these random numbers. If the random numbers were i, j and k, then adequate sample quantity from each of the containers that were numbered as i, j and k respectively were drawn. If the consignment was that of finished goods, then a sample with adequate quantity or minimum quantity was drawn as in the case of sampling from Retail Outlets/Government Sources. But, the difference here was that a sample was drawn from each formulation of each molecule provided that the molecule was in the list of 224 molecules. If a formulation had different batch numbers, then one sample from each batch was drawn. 130 Ministry of Health & Family Welfare National Drug Survey

17 National Institute of Biologicals (3) Packing the samples and posting them along with the Data Form to NIB after feeding the particulars in the AKS software. Primary Packaging: Primary Packing for each sample was to be completed at the Source. For the primary packaging, envelopes were supplied with the kit. One envelope per sample was used for packaging. Signature (with date) of all members of sample drawing team and authorised personnel of the Outlet were taken on primary package. Each sample was placed in the respective primary package and Sample Number, Batch Number, Manufacturing Date, Expiry Date, Name and Address of the manufacturer and quantity of the sample was written on the envelope. Open end of primary package was applied with adhesive and sealed with allotted brass seal at five places, two at the bottom, one at the middle and two at the top to maintain the integrity of the collected sample. Collection of Credit Bill: Since it was not a regulatory sample therefore each sample was paid for. Credit bill in favour of NIB, A-32, Sector 62, Institutional Area, NOIDA (U.P.) was collected for all the samples from each Source. Credit bills were verified and certified with full signature and date. Name and designation of the SDO were written in capital letters. Impression of the brass seal with unique number was also put on the Credit Bill to ensure traceability. One cancelled cheque was also collected from each Source to expedite payment through online transfer. Others: The Part- A and B of Data Form were filled in triplicate. Third copy of the filled Part -A and B were handed over to the authorised personnel of the Retail Outlet from where samples were drawn and an acknowledgement was taken from him on the first two copies. Sample drawing team was advised to take a photograph of the Source along with the team members and authorised personnel at the Retail Outlet, if possible (Exhibit 9.9). Sample drawing team, after collection, properly primary packaging and sealing all samples, left the Source and immediately proceeded to the next location as per the allotted list and followed the same procedure to draw samples. All the collected and sealed samples were thereafter kept in the safe custody of the respective SDOs. Ministry of Health & Family Welfare National Drug Survey

18 Main Survey Exhibit 9.9 Sample drawing teams at retail outlets in Kargil, Jammu & Kashmir and Goa 132 Ministry of Health & Family Welfare National Drug Survey

19 National Institute of Biologicals Feeding Sampling Data in AKS Software: After visiting all allotted Sources and drawing of all samples (six samples from each Source), the concerned SDOs fed the details of each collected sample on web portal of NIB ( NOIDA using AKS Software and took a print out for each sample. For this purpose, each SDO was provided with a unique user ID and password to access AKS Software. Secondary Packaging: Secondary packaging contained 6 items listed in Exhibit This content was wrapped with bubble wrap supplied with the kit-1 to protect the sample as well as the integrity of the seal. This wrapped content was placed in the secondary package envelope. Envelope was then closed and only sample ID was written on it. Tertiary Packaging: All secondary packages along with the brass seal were kept in the carton which was supplied in Kit-1. Sample numbers of all secondary packages were mentioned on this tertiary packaging. Ministry of Health & Family Welfare National Drug Survey

20 Main Survey EXHIBIT 9.10 Six Contents of Secondary Packaging 1. Primary packed sample 2. First copy of Data Form Part- A & B 3. Part C& D filled during sampling 4. Print out of form filled in AKS software 5. Original credit bill (in one of the secondary sample packs) 6. Photocopy of the credit bill and Data Form (in other secondary packs) Dispatch to NIB Tertiary packaging carton was forwarded to NIB through speed post (India Post) and cash receipt was obtained for reimbursement from NIB. SDOs were also to keep track through AKS software to ensure that samples were received at NIB. 134 Ministry of Health & Family Welfare National Drug Survey

21 National Institute of Biologicals RECEIPT OF SAMPLES AT NIB, VISUAL INSPECTION AND TRANSPORT OF SAMPLES TO LABORATORIES Receipt of samples at NIB A designated drug survey nodal officer of NIB received the samples from the various SDOs across the country and logged the details. A suitable storage area free from dust, pollutions, rodents, insects, excessive light, heat and humidity etc. was earmarked at NIB for storing the received samples. The storage area was air-conditioned and properly equipped with uninterrupted power (electrical) supply. Moreover, additional care was taken for photosensitive, hygroscopic and thermo sensitive samples. Visual Inspection All samples received at NIB were subjected to visual inspection and the institute provided all logistic support (Exhibit 9.11). For this purpose, Drugs Inspectors were deputed by CDSCO at NIB who were trained to carry out visual inspection as per the checklist of NIB and uplink their observations in AKS Software. Each Drugs Inspector was assisted by a bench biologist from NIB. The Drugs Inspectors checked if the samples were intact, broken or tampered. The samples as well as forms received along with it were verified for the Name of the Drug, Batch No., Manufacturing Date, Expiry Date, and Manufacturer s name etc. Thereafter, each sample was evaluated to answer the questions given in Exhibit AKS software had specific format on the questions given in exhibit 9.12 and all Drugs Inspectors were provided with unique ID and password to fill in the details of assigned samples in the format. Completion of visual inspection automatically updated the sample status in the AKS software as received and visually inspected at NIB. The sample showing major packaging and labelling defects were identified as suspects and were referred to CDSCO for further investigation. The major suspects were confirmed for authenticity with manufacturer by CDSCO officials to check whether the samples were Spurious under section 17B(d) of Drugs and Cosmetics Act, Ministry of Health & Family Welfare National Drug Survey

22 Main Survey Exhibit 9.11 Segregation and visual inspection of sample being done at NCC-NIB, Noida 136 Ministry of Health & Family Welfare National Drug Survey

23 National Institute of Biologicals Exhibit 9.12 Visual Inspection of Samples Received At NIB Observation Yes No Remarks Is outer carton have same color shade? Is printing on all packages of a sample is in uniform calligraphy? Does the label on the carton matches label on the container? Is the printing quality on the label satisfactory? Do the container/packaging protect the Drug from outside environment Do all samples have hologram? Do printed and plain foils have same shade? Are active ingredient s name spelled correctly on the label? Is manufacturer s name and logo uniform on all samples? Is printing of batch details legible? Is the composition expressed correctly and uniformly on all samples? Segregation of samples Drugs Inspectors, after completing visual inspection, divided the samples into two parts. First part was called primary. This part was stored at NIB as control sample. Second part, called secondary sample or test sample, was repacked and was meant for test/analysis by 10 Central/State Govt. Drug Testing Laboratories. However, in some cases the minimum adequate quantity of samples were received. In such cases, control quantity was not retained and the entire sample was sent for laboratory test/analysis. Transport of samples to Drug testing laboratories Analysis of the samples were carried out at selected Central/State Govt. Drug Testing Laboratories (Exhibit 9.13). Before dispatching to the Laboratory, all the samples were properly repacked. The relevant details of the samples were also inserted in the pack for the information of laboratory analyst. Samples were sent to selected testing laboratory through speed post. The samples details Ministry of Health & Family Welfare National Drug Survey

24 Main Survey were also transmitted online to respective laboratories through AKS software. This ensured that the laboratory personnel received the sample details earlier than physical receipt of sample. For this purpose, each laboratory was provided with unique ID and password to access AKS Software. The laboratory staff used this ID to acknowledge the receipt of samples from NIB and verify the details of the sample. Laboratory staff, however, was only provided with details (through online as well as hard copy) which were relevant for testing of samples. They were blinded to information related to area of collection or the details of the SDOs. Exhibit 9.13 Central/State Govt. Drug Testing Laboratories Selected For Drug Survey S. NO. NAME LOCATION CENTRAL LABORATORIES 1) Central Drugs Testing Laboratory Mumbai, Maharashtra 2) Central Drugs Laboratory Kolkata, West Bengal 3) Central Drugs Testing Laboratory Chennai, Tamil Nadu 4) Central Drugs Testing Laboratory Hyderabad, Telangana 5) Regional Drugs Testing Laboratory Guwahati, Assam 6) Regional Drugs Testing Laboratory Chandigarh 7) Indian Pharmacopoeia Commission Ghaziabad, Uttar Pradesh STATE LABORATORIES 8) Drugs Control Laboratory Mumbai, Maharashtra 9) Drug Testing Laboratory Bengaluru, Karnataka 10) Food and Drugs Laboratory Vadodara, Gujarat RECEIPT OF SAMPLES, TESTING AND REPORTING OF RESULTS BY LABORATORIES Receipt The samples sent by NIB through speed posts were received by respective laboratories. The authorised personnel of the laboratory were then to verify 138 Ministry of Health & Family Welfare National Drug Survey

25 National Institute of Biologicals the content and details of the sample and acknowledge the receipt of samples from NIB through AKS software. The details of the sample provided to the laboratory staff included minimum information required for performing quality test/analysis. Test/Analysis Methods and Specifications Indian Pharmacopoeia (IP) is the statutory document providing standards of quality of pharmaceuticals. The specifications and test methods applicable to collected Drug samples as per its monograph in IP/other Pharmacopoeia/ manufacturer s protocol were used for laboratory analysis as applicable. Reporting of results After completion of tests, the analysts reported results for every sample using AKS software mentioning all the specifications and compliance/noncompliance to the same. Based on the results, reports contained conclusion whether sample was of Standard Quality/Not of Standard Quality (NSQ). In the remarks column of the report, the reasons for declaring the sample as NSQ were noted. The report was transmitted to NIB by uploading it to the AKS software. Samples which failed in identification by respective drug testing laboratories were declared Spurious under section 17B(d) of Drugs and Cosmetics Act, NIB maintained a record of all test reports. Details of samples found to be Spurious and NSQ were also shared with appropriate regulatory authority. Ministry of Health & Family Welfare National Drug Survey

26