BIOLOGICAL E. LIMITED, HyderabadS. No Product PAC Details Date of NOC

1

DTwP-HepB-Hib Vaccine (Liquid

Pentavalent Vaccine)

01. Addition of new fermenter for production of Tetanus bulk antigen.

12.07.13

(NOC F.No: 12-52/BIO.E/PAC-EQUIP/13-BD)

02. Addition of new fermenter for production of Diphtheria bulk antigen.

12.07.13

(NOC F.No: 12-54/BIO.E/PAC-EQUIP (DT)/13-BD)

03. Change in Diphtheria bulk manufacturing process (Inactivation using Lysine)

10.01.14(NOC F.No: 12-106/Bio.E/PAC-Diphtheria (Bulk)/13-BD)

04. Deletion of Hib immunogenicity test at final bulk/lot of Liquid Pentavalent Vaccine. 23.05.14

(NOC F.No: 12-07/Bio.E/PAC-DTaP-Hep.B+ Hib/14-BD)

05. Architect kit for estimation of antigen content in Hepatitis-BPurified Bulk.

23.07.14

(NOC F.No: 12-22/Bio.E/(PAC-Hepatitis B-Bulk)/13-BD)

06. Replacement of Westfalia Centrifuge for manufacturing of Hepatitis B purified Bulk

01.12.14

(NOC F.No: 12-43/BIO.E/PAC-Hep.B(Bulk)/14-BD)

07. Addition of fermentor for manufacturing of Haemophilus influenzae type b vaccine bulk conjugate (HITT).

09.12.14

(NOC No: 12-58/BIO.E/PAC-HITT/14-BD)

08. Addition of new vial filling line (Line III) at Shameerpet site.

07.01.16

(NOC No: 12-100/Bio.E /PAC-Many Vaccines/15-BD)

09. Extension of shelf life of Tetanus toxoid carrier protein (CPTT) from 1 to 2 years.

01.12.15

(NOC No: 12-111/Bio.E/PAC-TT/15-BD)

10. Extension of shelf life of Liquid Pentavalent Vaccine from 24 to 30 months.

01.03.16

(NOC No: 12-125/Bio.E/PAC-DTwP-rHepB Hib Vac/15-BD)

11. Additional presentation (Pre-filled Syringe) - Liquid Pentavalent Vaccine

08.03.16

(NOC No: 12-09/BIO.E/PAC-DTP/16-BD)

12. Replacement of HBsAg kit with Adaltis kit for estimation of - antigen content in Hepatitis-B purified bulk and- testing of identity, % adsorption and in-vitro potency/antigen content in Liquid Pentavalent Vaccine

26.04.16

(NOC No: 12-25/Bio-E Ltd/PAC-Hep-B/16-BD)

13. Deletion of potency test from release specification of Whole cell Pertussis bulk.

28.03.16

(NOC No: 12-33/Bio-E Ltd/PAC-Pertussis/16-BD)

14. Addition of Fermenter & changes in downstream process in the manufacturing of Hepatitis B purified Bulk

25.05.16

(NOC No: 12-39/Bio-E ltd/PAC-HBPB/16-BD)

15. Use of pre-filtration and sterile filtration for Bulk Purified Diphtheria Toxoid (BPDT); use of capsule filters instead of cartridge filtration skid. 09.05.16

(NOC No: 12-43/Bio-E ltd/PAC-BPDT/16-BD)

16. Use of In-house prepared aluminium phosphate gel for Liquid Pentavalent Vaccine.

13.07.16

(NOC No: 12-71/Bio-E ltd/PAC-Pentavalent/16-BD)

17. Deletion of specific toxicity testing of Diphtheria and Tetanus components in final bulk/ final lot specifications.

30.06.16

(NOC No: 12-105/Bio-E ltd/PAC-Many Vac/16-BD)

18. Deletion of abnormal toxicity/general safety (Innocuity) test in final lot specifications.

30.06.16

(NOC No: 12-106/Bio-E ltd/PAC-Many Products/16-BD)

19. Approval of In-House Reference Standard (IHRS) of Pertussis for potency estimation in pertussis bulk.

30.08.16

(NOC No: 12-115/Bio. E.Ltd/PAC-Pertussis/16BD)

20. Approval for the following changes in Bulk Purified Tetanus Toxoid.- detoxification of concentrated tetanus toxin using 0.5% w/v L-Lysine HCl in addition to the existing detoxification process; - pre-filtration of purified tetanus toxoid using 0.5µ capsule filter; - sterile filtration of bulk purified tetanus toxoid using dual membrane capsule filters (0.4µ + 0 .2µ) & - introduction of re-processing step in sterile filtration of bulk purified tetanus toxoid.

23.09.16

(NOC No: 12-96/Bio-E Itd/PAC-BPTT/16-BD)

21. Approval of working seed bank (WCB) extended beyond an approved passage level (Clostridium Tetani, Harvard strain-49205)

23.09.16

(NOC No: 12-87/Bio-E. Ltd/PAC-TT/16-BD)

2 TT Vaccine 01. Addition of new fermenterfor production of Tetanus bulk antigen.

12.07.13

(NOC F.No: 12-52/BIO.E/PAC-EQUIP/13-BD)

02. Addition of new vial filling line (Line III) at Shameerpet site.

07.01.16

(NOC No: 12-100/Bio.E /PAC-Many Vaccines/15-BD)

03. Deletion of specific toxicity testing of Tetanus component in final bulk/ final lot specifications.

30.06.16

(NOC No: 12-105/Bio-E ltd/PAC-Many Vac/16-BD)

04. Deletion of abnormal toxicity/general safety (Innocuity) test in final lot specifications.

30.06.16

(NOC No: 12-106/Bio-E ltd/PAC-Many Products/16-BD)

05. Approval for the following changes in Bulk Purified Tetanus Toxoid.- detoxification of concentrated tetanus toxin using 0.5% w/v L-Lysine HCl in addition to the existing detoxification process; - pre-filtration of purified tetanus toxoid using 0.5µ capsule filter; - sterile filtration of bulk purified tetanus toxoid using dual membrane capsule filters (0.4µ + 0 .2µ) & - introduction of re-processing step in sterile filtration of bulk purified tetanus toxoid.

23.09.16

(NOC No: 12-96/Bio-E Itd/PAC-BPTT/16-BD)

06. Increasing the batch size upto 2000L for TT Vaccine (I.P), TT vaccine (B.P) and Td Vaccine

25.10.16

(NOC No: 12-138/Bio-E Itd/PAC-TT&TD/16-BD)

3

Td Vaccine 01. Addition of new fermenter for production of Tetanus bulk antigen.

12.07.13(NOC F.No: 12-52/BIO.E/PAC-EQUIP/13-BD)

02. Addition of new fermenter for production of Diphtheria bulk antigen.

12.07.13

(NOC F.No: 12-54/BIO.E/PAC-EQUIP (DT)/13-BD)

03. Change in Diphtheria bulk manufacturing process (Inactivation using Lysine)

10.01.14

(NOC F.No: 12-106/Bio.E/PAC-Diphtheria (Bulk)/13-BD)

04. Addition of new vial filling line (Line III) at Shameerpet site.

07.01.16

(NOC No: 12-100/Bio.E /PAC-Many Vaccines/15-BD)

05. Use of pre-filtration and sterile filtration for Bulk Purified Diphtheria Toxoid (BPDT); use of capsule filters instead of cartridge filtration skid.

09.05.16

(NOC No: 12-43/Bio-E ltd/PAC-BPDT/16-BD)

06. Deletion of specific toxicity testing of Diphtheria and Tetanus components in final bulk/ final lot specifications.

30.06.16

(NOC No: 12-105/Bio-E ltd/PAC-Many Vac/16-BD)

07. Deletion of abnormal toxicity/general safety (Innocuity) test in final lot specifications.

30.06.16

(NOC No: 12-106/Bio-E ltd/PAC-Many Products/16-BD)

08. Approval for the following changes in Bulk Purified Tetanus Toxoid.- detoxification of concentrated tetanus toxin using 0.5% w/v L-Lysine HCl in addition to the existing detoxification process; - pre-filtration of purified tetanus toxoid using 0.5µ capsule filter; - sterile filtration of bulk purified tetanus toxoid using dual membrane capsule filters (0.4µ + 0 .2µ) & - introduction of re-processing step in sterile filtration of bulk purified tetanus toxoid.

23.09.16

(NOC No: 12-96/Bio-E Itd/PAC-BPTT/16-BD)

09. Approval of working seed bank (WCB) extended beyond an approved passage level (Clostridium Tetani, Harvard strain-49205) 23.09.16

(NOC No: 12-87/Bio-E. Ltd/PAC-TT/16-BD)

10. Increasing the batch size upto 2000L for TT Vaccine (I.P), TT vaccine (B.P) and Td Vaccine

25.10.16

(NOC No: 12-138/Bio-E Itd/PAC-TT&TD/16-BD)

4

DTP Vaccine 01. Addition of new fermenterfor production of Tetanus bulk antigen.

12.07.13(NOC F.No: 12-52/BIO.E/PAC-EQUIP/13-BD)

02. Addition of new fermenter for production of Diphtheria bulk antigen.

12.07.13

(NOC F.No: 12-54/BIO.E/PAC-EQUIP (DT)/13-BD)

03. Change in Diphtheria bulk manufacturing process (Inactivation using Lysine)

10.01.14

(NOC F.No: 12-106/Bio.E/PAC-Diphtheria (Bulk)/13-BD)

04. Addition of new vial filling line (Line III) at Shameerpet site.

07.01.16

(NOC No: 12-100/Bio.E /PAC-Many Vaccines/15-BD)

05. Deletion of potency test from release specification of Whole cell Pertussis Antigen bulk.

28.03.16

(NOC No: 12-33/Bio-E Ltd/PAC-Pertussis/16-BD)

06. Use of pre-filtration and sterile filtration for Bulk Purified Diphtheria Toxoid(BPDT); use of capsule filters instead of cartridge filtration skid. 09.05.16

(NOC No: 12-43/Bio-E ltd/PAC-BPDT/16-BD)

07. Deletion of specific toxicity testing of Diphtheria and Tetanus components in final bulk/ final lot specifications.

30.06.16

(NOC No: 12-105/Bio-E ltd/PAC-Many Vac/16-BD)

08. Deletion of abnormal toxicity/general safety (Innocuity) test in final lot specifications.

30.06.16

(NOC No: 12-106/Bio-E ltd/PAC-Many Products/16-BD)

09. Approval of In-House Reference Standard (IHRS) of Pertussis for potency estimation in pertussis bulk.

30.08.16

(NOC No: 12-115/Bio. E.Ltd/PAC-Pertussis/16BD)

10. Approval for the following changes in Bulk Purified Tetanus Toxoid.- detoxification of concentrated tetanus toxin using 0.5% w/v L-Lysine HCl in addition to the existing detoxification process; - pre-filtration of purified tetanus toxoid using 0.5µ capsule filter; - sterile filtration of bulk purified tetanus toxoid using dual membrane capsule filters (0.4µ + 0 .2µ) & - introduction of re-processing step in sterile filtration of bulk purified tetanus toxoid.

23.09.16

(NOC No: 12-96/Bio-E Itd/PAC-BPTT/16-BD)

11. Approval of working seed bank (WCB) extended beyond an approved passage level (Clostridium Tetani, Harvard strain-49205) 23.09.16

(NOC No: 12-87/Bio-E. Ltd/PAC-TT/16-BD)

5

JE Vaccine 01. Additional presentation for JE vaccine (3 mcg/0.5 mL) for use in Pediatrics aged between 1-3 years.

14.11.13

(NOC F.No: 12-73/BIO.E/PAC-JE/13-BD)

02. Shelf life extension for JE vaccine (6µg/0.5mL) from 24 to 36 months

27.01.14

(NOC F.No: 12-111/Bio.E/(PAC-JE)/13-BD)

03. Change in supplier of Fetal Bovine Serum for JE bulk manufacturing.

15.10.14

(NOC No: 4-98/Biological.E/PAC-R/Fetal Calf Serum/14-BD)

04. Inclusion of booster dose for JE Vaccine

24.02.15

(NOC No: 12-67/Bio.E/PAC-JE Vaccine/14-BD)

05. Label expansion to include ≥ 3 to < 18 years age group in pack insert & SPC of JE vaccine.

27.05.15

(NOC No: 12-104/Bio.E / PAC-JE Vaccine/14-BD)

06. Addition of new vial filling line (Line III) at Shameerpet site.

07.01.16

(NOC No: 12-100/Bio.E /PAC-Many Vaccines/15-BD)

07. Additional presentation (Pre-filled Syringe) – JE Vaccine (3µg/0.5 mL)

09.02.16

(NOC No: 12-08/Bio·E/PAC-JE/16-BD)

08. Additional presentation (Pre-filled Syringe) – JE Vaccine (6µg/0.5 mL)

10.02.16

(NOC No: 12-10/Bio-E/PAC-JE/16-BD)

09. Deletion of abnormal toxicity/general safety (Innocuity) test in final lot specifications.

30.06.16

(NOC No: 12-106/Bio-E ltd/PAC-Many Products/16-BD)

6

DTwP-HepB+Hib Vaccine (Reconstituted Pentavalent Vaccine)

01. Addition of new fermenter for production of Tetanus bulk antigen.

12.07.13(NOC F.No: 12-52/BIO.E/PAC-EQUIP/13-BD)

02. Addition of new fermenter for production of Diphtheria bulk antigen.

12.07.13

(NOC F.No: 12-54/BIO.E/PAC-EQUIP (DT)/13-BD)

03. Change in Diphtheria bulk manufacturing process (Inactivation using Lysine)

10.01.14

(NOC F.No: 12-106/Bio.E/PAC-Diphtheria (Bulk)/13-BD)

04. Architect kit for estimation of antigen content in Hepatitis-B Purified Bulk.

23.07.14

(NOC F.No: 12-22/Bio.E/(PAC-Hepatitis B-Bulk)/13-BD)

05. Replacement of Westfalia Centrifuge for manufacturing of Hepatitis B purified Bulk

01.12.14

(NOC F.No: 12-43/BIO.E/PAC-Hep.B(Bulk)/14-BD)

06. Addition of fermentor for manufacturing of Haemophilus influenzae type b vaccine bulk conjugate (HITT).

09.12.14

(NOC No: 12-58/BIO.E/PAC-HITT/14-BD)

07. Addition of new vial filling line (Line III) at Shameerpet site.

07.01.16

(NOC No: 12-100/Bio.E /PAC-Many Vaccines/15-BD)

08. Extension of shelf life of Tetanus toxoid carrier protein (CPTT) from 1 to 2 years.

01.12.15

(NOC No: 12-111/Bio.E/PAC-TT/15-BD)

09. Replacement of HBsAg kit with Adaltis kit for estimation of antigen content in Hepatitis-B purified bulk

26.04.16

(NOC No: 12-25/Bio-E Ltd/PAC-Hep-B/16-BD)

10. Deletion of potency test from release specification of Whole cell Pertussis bulk.

28.03.16

(NOC No: 12-33/Bio-E Ltd/PAC-Pertussis/16-BD)

11. Addition of Fermenter &changes in downstream process in the manufacturing of Hepatitis B purified Bulk

25.05.16

(NOC No: 12-39/Bio-E ltd/PAC-HBPB/16-BD)

12. Use of pre-filtration and sterile filtration for Bulk Purified Diphtheria Toxoid(BPDT); use of capsule filters instead of cartridge filtration skid. 09.05.16

(NOC No: 12-43/Bio-E ltd/PAC-BPDT/16-BD)

13. Deletion of specific toxicity testing of Diphtheria and Tetanus components in final bulk/ final lot specifications.

30.06.16

(NOC No: 12-105/Bio-E ltd/PAC-Many Vac/16-BD)

14. Deletion of abnormal toxicity/general safety (Innocuity) test in final lot specifications.

30.06.16

(NOC No: 12-106/Bio-E ltd/PAC-Many Products/16-BD)

15. Approval of In-House Reference Standard (IHRS) of Pertussis for potency estimation in pertussis bulk.

30.08.16

(NOC No: 12-115/Bio. E.Ltd/PAC-Pertussis/16BD)

16. Approval for the following changes in Bulk Purified Tetanus Toxoid.- detoxification of concentrated tetanus toxin using 0.5% w/v L-Lysine HCl in addition to the existing detoxification process; - pre-filtration of purified tetanus toxoid using 0.5µ capsule filter; - sterile filtration of bulk purified tetanus toxoid using dual membrane capsule filters (0.4µ + 0 .2µ) & - introduction of re-processing step in sterile filtration of bulk purified tetanus toxoid.

23.09.16

(NOC No: 12-96/Bio-E Itd/PAC-BPTT/16-BD)

17. Approval of working seed bank (WCB) extended beyond an approved passage level (Clostridium Tetani, Harvard strain-49205)

23.09.16

(NOC No: 12-87/Bio-E. Ltd/PAC-TT/16-BD)

7

Hepatitis B Vaccine (rDNA)

01. Architect kit for estimation of antigen content in Hepatitis-B Purified Bulk.

23.07.14(NOC F.No: 12-22/Bio.E/(PAC-Hepatitis B-Bulk)/13-BD)

02. Replacement of Westfalia Centrifuge for manufacturing of Hepatitis B purified Bulk

01.12.14

(NOC F.No: 12-43/BIO.E/PAC-Hep.B(Bulk)/14-BD)

03. Addition of new vial filling line (Line III) at Shameerpet site.

07.01.16

(NOC No: 12-100/Bio.E /PAC-Many Vaccines/15-BD)

04. Replacement of HBsAg kit with Adaltis kit for estimation of - antigen content in Hepatitis-B purified bulk and- testing of identity, % adsorption and in-vitro potency/antigen content in Hepatitis B Vaccine

26.04.16

(NOC No: 12-25/Bio-E Ltd/PAC-Hep-B/16-BD)

05. Addition of Fermenter &changes in downstream process in the manufacturing of Hepatitis B purified Bulk

25.05.16

(NOC No: 12-39/Bio-E ltd/PAC-HBPB/16-BD)

06. Deletion of abnormal toxicity/general safety (Innocuity) test in final lot specifications.

30.06.16

(NOC No: 12-106/Bio-E ltd/PAC-Many Products/16-BD)

8

Haemophilus Type b Conjugate Vaccine

01. Addition of fermentor for manufacturing of Haemophilus influenzae type b vaccine bulk conjugate (HITT).

09.12.14

(NOC No: 12-58/BIO.E/PAC-HITT/14-BD)

02. Addition of new vial filling line (Line III) at Shameerpet site.

07.01.16

(NOC No: 12-100/Bio.E /PAC-Many Vaccines/15-BD)

03. Extension of shelf life of Tetanus toxoid carrier protein (CPTT) from 1 to 2 years.

01.12.15

(NOC No: 12-111/Bio.E/PAC-TT/15-BD)

04. Deletion of abnormal toxicity/general safety (Innocuity) test in final lot specifications.

30.06.16

(NOC No: 12-106/Bio-E ltd/PAC-Many Products/16-BD)

9

DTPH(Tetravalent Vaccine)

01. Addition of new fermenterfor production of Tetanus bulk antigen.

12.07.13(NOC F.No: 12-52/BIO.E/PAC-EQUIP/13-BD)

02. Addition of new fermenter for production of Diphtheria bulk antigen.

12.07.13

(NOC F.No: 12-54/BIO.E/PAC-EQUIP (DT)/13-BD)

03. Change in Diphtheria bulk manufacturing process (Inactivation using Lysine)

10.01.14

(NOC F.No: 12-106/Bio.E/PAC-Diphtheria (Bulk)/13-BD)

04. Architect kit for estimation of antigen content in Hepatitis-B Purified Bulk.

23.07.14

(NOC F.No: 12-22/Bio.E/(PAC-Hepatitis B-Bulk)/13-BD)

05. Replacement of Westfalia Centrifuge for manufacturing of Hepatitis B purified Bulk

01.12.14

(NOC F.No: 12-43/BIO.E/PAC-Hep.B(Bulk)/14-BD)

06. Addition of new vial filling line (Line III) at Shameerpet site.

07.01.16

(NOC No: 12-100/Bio.E /PAC-Many Vaccines/15-BD)

07. Replacement of HBsAg kit with Adaltis kit for estimation of antigen content in Hepatitis-B purified bulk

26.04.16

(NOC No: 12-25/Bio-E Ltd/PAC-Hep-B/16-BD)

08. Deletion of potency test from release specification of Whole cell Pertussis bulk.

28.03.16

(NOC No: 12-33/Bio-E Ltd/PAC-Pertussis/16-BD)

09. Addition of Fermenter & changes in downstream process in the manufacturing of Hepatitis B purified Bulk

25.05.16

(NOC No: 12-39/Bio-E ltd/PAC-HBPB/16-BD)

10. Use of pre-filtration and sterile filtration for Bulk Purified Diphtheria Toxoid (BPDT); use of capsule filters instead of cartridge filtration skid.

09.05.16

(NOC No: 12-43/Bio-E ltd/PAC-BPDT/16-BD)

11. Deletion of specific toxicity testing of Diphtheria and Tetanus components in final bulk/ final lot specifications.

30.06.16

(NOC No: 12-105/Bio-E ltd/PAC-Many Vac/16-BD)

12. Deletion of abnormal toxicity/general safety (Innocuity) test in final lot specifications.

30.06.16

(NOC No: 12-106/Bio-E ltd/PAC-Many Products/16-BD)

13. Approval of In-House Reference Standard (IHRS) of Pertussis for potency estimation in pertussis bulk.

30.08.16

(NOC No: 12-115/Bio. E.Ltd/PAC-Pertussis/16BD)

14. Approval for the following changes in Bulk Purified Tetanus Toxoid.- detoxification of concentrated tetanus toxin using 0.5% w/v L-Lysine HCl in addition to the existing detoxification process; - pre-filtration of purified tetanus toxoid using 0.5µ capsule filter; - sterile filtration of bulk purified tetanus toxoid using dual membrane capsule filters (0.4µ + 0 .2µ) & - introduction of re-processing step in sterile filtration of bulk purified tetanus toxoid.

23.09.16

(NOC No: 12-96/Bio-E Itd/PAC-BPTT/16-BD)

15. Approval of working seed bank (WCB) extended beyond an approved passage level (Clostridium Tetani, Harvard strain-49205)

23.09.16

(NOC No: 12-87/Bio-E. Ltd/PAC-TT/16-BD)