PREPARATION

VACCINE AND SERA

GROUP : III
• NENSI HARTATI 1511012011
• MELISA OKTAVIA 1511012021
• OLVI SEMARTHA 1511012023
• FIANNY REZKA SJAHJADI 1511012027
• ALI AKBAR 1511012029
 Biological products can be defined according to their source material and
method of manufacture

Biological products are derived from cells, tissues or microorganisms and reflect
the inherent variability characteristic of living materials.

INTRODUCTI
ON The active substances in biological products are often too complex to be fully
characterized by utilizing physicochemical testing methods alone and may show a
marked heterogeneity from one preparation and/or batch to the next.

Consequently, special considerations are needed when manufacturing biological

products in order to maintain consistency in product quality.

(WHO, 2016: 96)

 Vaksin adalah sedian yang mengandung zat antigenik yang mampu
menimbulkan zat antigenik yang mampu menimbulkkan
kekebalan aktif dan khas pada manusia. Vaksin dibuat dari bakteri,
VACCINE risetsia atau virus dan dapat berupa suspense organisme hidup
atau inaktif atau fraksi-fraksinya atau toksoid

(Farmakope Indonesia Edisi IV)

 Live Attenuated virus Vaccines

• Ex : meningitis, tuberculosis, virus measles,

rubella

TYPE OF Inactivated/killed virus Vaccines

VACCINE • Ex : cbakteri kolera, pertusis, tifoid, virus

rabies, virus influenza

Subunit Vaccines

• Ex : Hepatitis B, Influenza

(Kistner, 2003)
  To produce a live vaccine, the wild or disease- causing virus is
attenuated (weakened), traditionally by repeated culture in the
laboratory,

Live  The virulence properties of the virus are reduced so that it does
not cause disease in healthy individuals. The attenuated vaccine
attenuated virus multiplies to a limited extent in host tissue and induces an
immune response similar to wild virus infection in the majority of
vaccines subjects. Live vaccines are generally very effective and induce
long-lived immunity.
 Eg. Measles, Mumps, Rubella, Varicella, Rotavirus, Tuberculosis
(BCG)

(Kistner, 2003)
  The term ‘killed’ is generally used for bacterial vaccines and
the term ‘inactivated’ for viral vaccines
 These vaccines are prepared by treating the whole cell or virus
Killed and with chemicals that cause inactivation
inactivated  Generally these organisms remain intact and whole

vaccines  They generate an immune response (to a broad range of antigens)

but cannot cause an infection because they are dead and so
cannot reproduce.
 Eg. Hepatitis A, Some influenza vaccines

(Kistner, 2003)
  Subunit vaccines are developed using only the antigens known to
elicit protective immunity.
Subunit  They can be further categorised as follows
vaccines  Eg : Hepatitis B, Influenza

(Kistner, 2003)
 1. Raw materials, pengambilan bibit vaksin terbaik
[virus/bakteri] agar jumlahnya memenuhi kebutuhan
pembuatan vaksin.
2. Cultivation & Harvest, penanaman virus/bakteri
pada media yang sudah dimurnikan
3. Purification, melakukan pemurnian virus/bakteri
Proses yang sudah tumbuh, dalam proses purifikasi, yaitu
Produksi suatu proses untuk menghilangkan zat – zat yang
tidak reevan dengan produk vaksin.
Vaksin 4. Formulation, memformulasikan bulk vaksin yang
telah dimurnikan dengan zat – zat tambahan
5. Filling, melakukan pengisian vaksin kedalam
kemasan
6. Packaging & Product, pemasangan label pada
kemasan
 The production of a vaccine can be divided in the following steps:
1. Generation of the antigen
- The first step in order to produce a vaccine is generating the
antigen that will trigger the immune response. For this purpose
the pathogen’s proteins or DNA need to be grown and harvested
Preparation of using the following mechanisms:

Vaccines - Viruses are grown on primary cells such as cells from chicken
embryos or using fertilised eggs (e.g. influenza vaccine) or cell
lines that reproduce repeatedly (e.g. hepatitis A)
- Bacteria are grown in bioreactors which are devices that use a
particular growth medium that optimises the production of the
antigens Recombinant proteins derived from the pathogen can
be generated either in yeast, bacteria or cell cultures.
 2. Release and isolation of the antigen
- After the antigen is generated, vaccines are isolated from
the cells, used to generate it. For weakened or attenuated viruses
no further purification may be required.
- The aim of this second step is to release as much virus or
bacteria as possible. To achieve this, the antigen will be separated
from the cells and isolated from the proteins and other parts of
the growth medium that are still present.
- Recombinant proteins need many operations involving
ultrafiltration and column chromatography for purification before
they are ready for administration.
 3. Addition of adjuvants, stabilizers and preservatives
- Once the antigen is developed the vaccine is formulated by
adding adjuvants, stabilizers, and preservatives.
- The role of the adjuvant is to enhance the immune response of
the antigen.
- The stabilizers increase the storage life.
- Preservatives allow the use of multi dose vials.
- Finally, all components that constitute the final vaccine are
combined and mixed uniformly in a single vial or syringe.
 4. Packaging
- Once the vaccine is put in recipient vessel (either a vial or a
syringe), it is sealed with sterile stoppers.
  Validation Stage I
 Validation Stage II
 Validation Stage III
Proses validasi  Revalidation
 Validation Studies and the WHO Pre-Qualification process
 Expectation
 • Process Description • Concentration
• Process Characterization • Inactivation and Detoxification
• Raw Materials / Starting • Clarification (pre-filtration)
Materials
• Viral clearance
• Extractables and Leachables
from Product-contact Surfaces • Chromatography resins and
reusable membranes
Validation • Seed Banks
• Buffer preparation
• Cell Lines and Cell Banks
Stage I • Analytical Methods
• Process Intermediates
• Blending (polyvalent vaccines)
• Validation of production Steps
or Unit Operations • Formulation of Bulk Product
• Propagation
• Fermentation
• Harvest
  Definition of Operational Parameters at commercial scale
 Manufacturing of Consistency Lots
 Consistency Lots
 Manufacturing of Clinical Phase Material
 Bracketing, Family and Matrix Validation Approach
 documentation Requirements
 personnel Training and Qualification
Validation  Process Technology Transfer
Stage II  Legacy products
 Design and Execution of Process Validation Studies
 Deviations Management
 Final Report
  Serum merupakan produk sebenarnya produk biologi yang sudah
mengandung kekebalan terhadap suatu infeksi.
 Serum diberikan kepada individu bila terserang adanya infeksi
penyakit, atau diduga akan terkena infeksi.
SERA  Salah satu contohnya adalah serum anti bisa ular (SABU) atau
snake anti venom merupakan produk biologis yang digunakan
dalam pengobatan gigitan ular berbisa.
 Anti bisa ular diberikan ketika seorang pasien terbukti atau diduga
telah digigit ular berbisa.

(Kemenkes RI. 2016)

• Serpentarium yang dikelola dengan baik adalah kunci dalam
produksi antivenom dan memenuhi persyaratan kualitas untuk
produksi yang antivenoms yang efektif.
• persiapan referensi sangat penting, Kualitas ular yang digunakan
untuk imunisasi hewan, sebagai bahan praklinis penilaian
efektivitas netralisasi, atau untuk pengembangan nasional atau
regional.
• Prosedur yang digunakan dalam pemeliharaan ular, penanganan
dan penambangan racun, serta dalam semua aspek pengumpulan
racun harus didokumentasikan dan dijadwalkan dengan benar.

WHO Guidelines for the Production Control and Regulation

of Snake Antivenom Immunoglobulins
 Venom yang digunakan untuk preparasi antivenom
harus mewakili seluruh populasi ular yang hidup di area
di mana antena polispesifik dan / atau monospesifik
dimaksudkan untuk digunakan.
 Karena variasi regional dan individu dalam komposisi
racun dalam spesies ular, venoms yang digunakan
untuk imunisasi harus dikumpulkan dari sejumlah besar
individu (umumnya setidaknya 20, termasuk jantan
dan betina dari berbagai usia) yang dikumpulkan dari
berbagai daerah yang mencakup seluruh distribusi
geografis dari spesies ular berbisa tertentu.

WHO Guidelines for the Production Control and Regulation

of Snake Antivenom Immunoglobulins
  Kontrol kualitas dari venoms ular sangat penting untuk
memberikan jaminan bahwa venoms mewakili ular
berbisa yang mendiami wilayah tempat antivenoms
diproduksi.
Quality control  Kumpulan Rumpun Referensi Nasional harus
of venoms ditetapkan untuk mencakup setiap spesies ular yang
penting secara medis di mana antivenom diproduksi.
 Keterlacakan setiap kumpulan racun penting untuk
mendeteksi secara cepat setiap kesalahan yang
mungkin terjadi selama proses persiapan.

WHO Guidelines for the Production Control and Regulation of Snake

Antivenom Immunoglobulins
 Untuk setiap kumpulan racun, sertifikasi yang menyatakan nama
ilmiah spesies ular (dan subspesies jika ada), asal geografis mereka
dan jumlah hewan yang digunakan dalam mengumpulkan bets,
tanggal pengumpulan racun, dan lainnya yang relevan
 informasi, harus disediakan oleh pemasok racun ke produsen
antivenom dan juga kepada otoritas pengatur jika diperlukan.

WHO Guidelines for the Production Control and Regulation of

Snake Antivenom Immunoglobulins
 Konsistensi (dalam batasan komposisi dan kualitas yang
ditetapkan) kumpulan racun yang dihasilkan dari waktu ke waktu
untuk spesies berbisa yang sama dengan asal yang sama harus
dijamin.
 Tes khusus harus dilakukan di setiap sampel racun, dan
datadicatat untuk dilacak, termasuk: konsentrasi protein per g
(atau mg),
 suatupenilaian aktivitas biokimia atau biologis, pemindaian atau
gambar dari SDS – PAGE (dalam kondisi pengurangan dan tanpa-
reduksi), dan / atau profil kromatografi HPLC fase balik atau
ukuran mundur dari sampel racun. Informasi ini terbukti berguna
untuk mengkonfirmasi asal dan integritas racunnya.

WHO Guidelines for the Production Control and Regulation of

Snake Antivenom Immunoglobulins
 VACCINE
 Vaccine is an antigenic substance prepared from the causative
agent of a disease or a synthetic substitute, used to provide
immunity against one or several diseases.

Difference  Contains dead bacteria or weak bacteria or toxins.

 stimulates the body to make antioxidants
Between
 Gaining immunity after a period.
Vaccines and  Remain immune for long.
Sera  Use a series of complex methods to separate and purify the virus
and extract the required part, reduce the low virulent or
inactivated and produced vaccine.
 A vaccine consists of normally a single type of antibodies( usually
monoclonal) or may be for a particular disease
SERA
 The clear, pale yellow liquid that separates from the clot in the
coagulation of blood
 does not contain bacteria or toxins.
 contains anti formed in another animal.
 acquired immune immediately.
 remain a short time.
 specific animal by immunization, whole blood collected in, but the
serum is a nonspecific mixture obtained after centrifugation.
  CDC, 2014. Vaccine Storage and Handling Toolkit. Atlanta: CDC
 Departemen Kesehatan RI, Farmakope Indonesia, Edisi IV, 1995
 Kemenkes RI. 2016. Vaksin Untuk Pencegahan, Serum Untuk
Pengobatan. www.depkes.go.id
 Kistner, Otfried, Baxter Vaccine AG, “A Novel Cell-Derived
Influenza Vaccine, National Influenza Summit, Chicago, May 20-
21, 2003
Daftar pustaka  Dept. of Pharmacognosy Shri D.D Vispute College of Pharmacy
 Sugiarto. 2013. Vaksin.
 WHO Guidelines for the Production Control and Regulation of
Snake Antivenom Immunoglobulins
 WHO. 2013.Validation of Production Processes for Vaccines for
WHO Prequalification- Compliance Expectations :Switzerland
 WHO. 2016. WHO good manufacturing practices for biological
products. WHO Expert Committee on Biological Standardization