biotechnology product - prevnar

1 By Omita Trivedi and Neha Gandhi

Biotechnology applies scientific disciplines including chemistry, engineering, physics

and computing to living organisms to create innovative products and techniques.

Health Biotechnology is the largest sector of biotechnology that creates products

Including therapies and drugs, vaccines and new diagnostic and testing equipment.

Therapeutics – new biologic drugs include skin grown for burn victims, gene and stem cell

therapies, new drugs and personalized medicine

Diagnostics –test kits for HIV, or diabetes provide new, lower cost, options to test for devastating diseases quickly and effectively

Medical Devices– biosensors, stents, prostheses

Vaccines - over 25 companies make innovative vaccines for childhood and adult diseases

2

By Omita Trivedi and Neha Gandhi

Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein), Prevnar®,

is a sterile solution of saccharides of the capsular antigens of Streptococcus

pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F individually conjugated to

diphtheria CRM197 protein.

At least 90 Capsular Serotypes are known based on the structural

and chemical structure of the capsular polysaccharides

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S. pneumoniae is an important cause of morbidity and mortality in persons of all

ages worldwide. The organism causes invasive infections, such as bacteremia and

meningitis, as well as pneumonia and upper respiratory tract infections including

otitis media and sinusitis. In children older than 1 month, S. pneumoniae is the most

common cause of invasive disease.

Every year in Canada, over half a million cases of pneumococcal disease are reported in infants and children, and thousands of Canadian children will undergo ear tube insertion to treat otitis media. The total annual treatment costs for pneumococcal disease amounts to nearly 200 million dollars a year.

Increased resistance to penicillin and other important classes of antimicrobials has complicated the management of S. pneumoniae infections in recent years

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People at increased risk • Children aged under two years • Children under five years with underlying medical conditions predisposing them to

invasive pneumococcal disease • Indigenous children, especially in central Australia • People aged 65 years and over • People with weakened immune systems • People with chronic diseases such as diabetes, lung disease, cancer or kidney disease • People who have impaired spleen function or have had their spleen removed • Tobacco smokers.

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The immune response to most antigens is T-dependent and involves the collaboration of CD4+ T-cells and B-cells, recognizing the antigen in a linked fashion.

CD4+ T-cells (T-helper cells) provide signals to B-cells directly through cell surface protein interactions, and indirectly through the release of cytokines. These signals result in proliferation and differentiation of the B-cells and production of high-affinity antibodies.

This also facilitates generation of memory B-cells that rapidly mobilize and secrete antibodies upon re-exposure to the same antigen.

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Pneumococcal capsular polysaccharides (PSs), while varied in chemical structure, are T-independent antigens. In the absence of T-cell help, PS stimulated B-cells predominantly produce IgM antibodies; and no memory B-cells are generated. As vaccines, PSs are associated with poor or absent immunogenicity in infants less than 24 months of age and failure to induce immunological memory at any age.

Conjugation of PSs to a protein carrier (CRM 197) overcomes the T-cell–independent nature of PS antigens. Protein carrier-specific T-cells provide the signals needed for maturation of the B-cell response and generation of B-cell memory.

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Efficacy was assessed in a randomized, double-blinded clinical trial in a

Multiethnic population at Northern California Kaiser Permanente (NCKP) from

October 1995 through August 20, 1998, in which 37,816 infants were randomized to

receive either Prevnar® or a control vaccine (an investigational meningococcal

group C conjugate vaccine [MnCC]) at 2, 4, 6, and 12-15 months of age.

Prevnar® was administered to 18,906 children and the control vaccine to 18,910

children.

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TABLE 1 Efficacy of Prevnar® Against Invasive Disease Due to S. pneumoniae in Cases Accrued From October 15, 1995 Through August 20, 1998 20,21

Prevnar® Number of Cases

Control* Number of Cases

Efficacy

95% CI

Vaccine serotypes

Per protocol 0 17 100% 75.4, 100

Intent-to-treat 0 22 100% 81.7, 100

All pneumococcal serotypes

Per protocol 2 20 90.0% 58.3, 98.9

Intent-to-treat

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http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=7abf4185-109d-4e3c-5da7-0b0658921637

Prevnar® is indicated for active immunization of infants and toddlers against

invasive disease caused by S. pneumoniae due to capsular serotypes included in

the vaccine (4, 6B, 9V, 14, 18C, 19F, and 23F).

The routine schedule is 2, 4, 6, and 12-15 months of age.

Prevnar® is also indicated for active immunization of infants and toddlers against

otitis media caused by serotypes included in the vaccine. However, for vaccine

serotypes, protection against otitis media is expected to be substantially lower than

protection against invasive disease.

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Hypersensitivity to any component of the vaccine, including diphtheria toxoid, is a contraindication to use of this vaccine. This vaccine will not protect against s. pneumoniae disease caused by serotypes unrelated to those in the vaccine, nor will it protect against other microorganisms that cause invasive infections such as bacteremia and meningitis or non-invasive infections such as otitis media. This vaccine should not be given to infants or children with thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injection unless the potential benefit clearly outweighs the risk of administration. If the decision is made to administer this vaccine to children with coagulation disorders, it should be given with caution. Immunization with Prevnar® does not substitute for routine diphtheria immunization.

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Prevnar® is for intramuscular use only. Prevnar® SHOULD UNDER NO

CIRCUMSTANCES BE ADMINISTERED INTRAVENOUSLY. The safety and

immunogenicity for other routes of administration (eg, subcutaneous) have not

been evaluated.

Fever, and rarely febrile seizure, have been reported in children receiving Prevnar®.

Minor illnesses, such as a mild respiratory infection with or without low-grade

fever, are not generally contraindications to vaccination. The administration of

Prevnar should be postponed in subjects suffering from acute severe febrile illness.

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Children receiving therapy with immunosuppressive agents (large amounts of

corticosteroids, antimetabolites, alkylating agents, cytotoxic agents) may not

respond optimally to active immunization.

As with other intramuscular injections, Prevnar® should be given with caution to

children on anticoagulant therapy.

Simultaneous Administration with Other Vaccines:

During clinical studies, Prevnar® was administered simultaneously with DTaP and

HbOC, IPV, Hep B vaccines, MMR, and Varicella vaccine. Thus, the safety

experience with Prevnar® reflects the use of this product as part of the routine

immunization schedule.

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The majority of the safety experience with Prevnar® comes from the NCKP Efficacy Trial in which 17,066 infants received 55,352 doses of Prevnar®, along with other Routine childhood vaccines through April 1998 Of the 17,066 subjects who received at least one dose of Prevnar® in the efficacy trial, there were: 24 hospitalizations (for 29 diagnoses) within 3 days of a dose from October 1995

through April 1998. 162 visits to the emergency room (for 182 diagnoses) within 3 days of a dose from

October 1995 through April 1998. Urticaria-like rash was reported in 1.3%-6% of children in the period from 3 to 14

days following immunization, and was most often reported following the fourth dose when it was administered concurrently with MMR vaccine.

One case of a hypotonic-hyporesponsive episode (HHE) was reported in the efficacy study following Prevnar® and concurrent DTP vaccines in the study period from October 1995 through April 1998.

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In the Kaiser efficacy study in which 17,066 children received a total of 55,352

Doses of Prevnar® and 17,080 children received a total of 55,387 doses of the

Control vaccine (investigational meningococcal group C conjugate vaccine

[MnCC]),

seizures were reported in 8 Prevnar® recipients and 4 control vaccine recipients

within 3 days of immunization from October 1995 through April 1998.

twelve deaths (5 SIDS and 7 with clear alternative cause) occurred among subjects receiving Prevnar®, of which 11 (4 SIDS and 7 with clear alternative cause) occurred in the Kaiser efficacy study from October 1995 until April 20, 1999.

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In addition to reports in clinical trials, the following adverse events have been reported

since market introduction of Prevnar® worldwide. The following adverse events were

included based on strength of causal association, severity, or frequency of reporting for

Prevnar®.

Administration site conditions: injection site dermatitis, injection site urticaria, injection site pruritus

Blood and lymphatic system disorders: lymphadenopathy localized to the region of the injection site

Immune system disorders: hypersensitivity reaction including face edema, dyspnea, bronchospasm; anaphylactic/anaphylactoid reaction including shock

Psychiatric disorders: crying

Skin and subcutaneous tissue disorders: angioneurotic edema, erythema multiforme

Respiratory: apnea

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For intramuscular injection only. Not to be injected intravenously.

The dose is 0.5 mL to be given intramuscularly.

The vaccine should be injected intramuscularly. The preferred sites are the

anterolateral aspect of the thigh in infants or

the deltoid muscle of the upper arm in toddlers and young children.

The vaccine should not be injected in the

gluteal area or

areas where there may be a major nerve trunk and/or blood vessel.

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Vaccination schedule for infants and toddlers

Dose: Dose 1*† Dose 2† Dose 3† Dose 4‡

Age at Dose: 2 months 4 months 6 months 12-15 months

* Dose 1 may be given as early as 6 weeks of age. † The recommended dosing interval is 4 to 8 weeks. ‡ The fourth dose should be administered at approximately 12-15 months of age, and at least 2 months after the third dose.

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Product Information Product Type – Vaccine

Route of Administration - Intramuscular

NDC Product Code (Source) – 0005-1970

Marketing Information

Marketing Category – BLA

Application Number - BLA103905

Marketing Start Date - 03/01/2000

Labeler

Wyeth Pharmaceutical Division of Wyeth Holdings Corporation, a subsidiary of

Pfizer Inc. (054065909)

Establishment Name

Wyeth Pharmaceutical Division of Wyeth Holdings Corporation, a subsidiary of Pfizer Inc.

ID/FEI – 883534067 - Manufacture, Analysis, API Manufacture

ID/FEI – 054065909 - Analysis, API Manufacture, Manufacture

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The 6 additional serotypes are 1, 3, 5, 6A, 7F, and 19A

Like Prevnar 7, Prevnar 13® does not provide 100% protection against vaccine serotypes or protect against nonvaccine serotypes.

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Prevnar 13® builds upon the scientific foundation of Prevnar® 7 by providing coverage against 6 additional serotypes that can cause IPD in young children. This includes serotype 19A, which is the leading cause of IPD in children less than 5 years of age and has become increasingly resistant to multiple antibiotics.

Approved for use in children 6 weeks through 5 years of age and for adults over 50 years of age.

The vast majority of Health Care Providers have converted to Prevnar 13.

Like Prevnar 7, Prevnar 13® does not provide 100% protection against vaccine serotypes or protect against nonvaccine serotypes.

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• For infants and toddlers, Prevnar 13 is to be administered as a four-dose series at 2, 4, 6, and 12-15 months of age.

• Children who have received one or more doses of Prevnar 7 may transition

to Prevnar 13 to complete the four-dose immunization series. • Children 15 months to 5 years of age who have received four doses of

Prevnar 7 may receive one dose of Prevnar 13 to elicit immune responses to the six additional serotypes.

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Prevnar 13 is to be administered as a single dose of 0.5 mL to adults 50 years and older including those previously vaccinated with a pneumococcal polysaccharide vaccine.

Overdose with Prevnar 13 is unlikely due to its presentation as a pre-filled syringe.

However, in infants and children there have been reports of overdose with Prevnar 13 defined as subsequent doses administered closer than recommended to the previous dose. In general, adverse events reported with overdose are consistent with those that have been reported with doses given in the recommended pediatric schedules of Prevnar 13.

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Product Information Product Type – Vaccine

Route of Administration - Intramuscular

NDC Product Code (Source) – 0005-1971

Marketing Information

Marketing Category – BLA

Application Number – BLA125324

Marketing Start Date - 03/01/2010

Labeler

Wyeth Pharmaceutical Division of Wyeth Holdings Corporation, a subsidiary of

Pfizer Inc. (054065909)

Establishment Name

Wyeth Pharmaceutical Division of Wyeth Holdings Corporation, a subsidiary of Pfizer Inc.

ID/FEI – 883534067 – API Manufacture, Analysis,

ID/FEI – 054065909 - Analysis, Manufacture

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1. http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=7abf4185-109d-4e3c-5da7-0b0658921637

2. http://www.biotech.ca/en/what-biotech-is/benefits.aspx

3. http://www.pfizerpro.com/resources/salesrep_private/minisites/prevnar/docs/PrevnarExitLetter.pdf

4. Kim et al. Analytical Biochemistry Vol 347, Issue 2, Pages 262–274

5. Pletz et. al. International Journal of Antimicrobial Agents, 2008

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http://www.biotech.ca/en/what-biotech-is/benefits.aspx





http://www.pfizerpro.com/resources/salesrep_private/minisites/prevnar/docs/PrevnarExitLetter.pdf

http://www.pfizerpro.com/resources/salesrep_private/minisites/prevnar/docs/PrevnarExitLetter.pdf

http://www.sciencedirect.com/science/journal/00032697

http://www.sciencedirect.com/science/journal/00032697/347/2



biotechnology product - prevnar

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